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LUDWIG LINK | APRIL 2021
LUDWIG
IN THIS ISSUE
4 | Breaking 18 | Q&A with
LINK
news Lana Kandalaft
Ludwig opens a new The challenges and
Branch at Princeton hopes of developing
APRIL 2021 University cancer vaccines
1
LIFE-CHANGING SCIENCE
ON THE COVER
As a lighter take on scientific illustration, this artwork was created to depict
Ludwig Harvard Co-director Joan Brugge’s study demonstrating that NRF2
hyperactivation, in cooperation with GPX4, maintains the survival of inner
matrix-deprived cells within 3-dimensional tumor spheroids by mitigating
ferroptosis, the lipid peroxidation-induced non-apoptotic cell death.
The illustration, by Rachel Davidowitz, depicts the fate of inner spheroid cells
in the presence or absence of NRF2 hyperactivation. Inner spheroid cells
(represented as wooden houses) are vulnerable to lipid peroxidation (fire),
compared to outer cells (brick houses). NRF2 hyperactivation (firefighter
LUDWIG LINK | APRIL 2021
with water hose) and GPX4 (firefighter with bucket of water) neutralize lipid
peroxidation, resulting in the formation of filled spheroid structures. You can
read about the study on Page 16.
2
LUDWIG LINK
ludwigcancerresearch.org APRIL 2021
LETTER
TABLE OF CONTENTS
Welcome to the spring issue of
Ludwig Link! BREAKING NEWS 4
A 50th anniversary splash 4
This season is said to be all Awards and distinctions 5
about new beginnings, so it’s For enduring contributions 5
fitting that Ludwig just launched For epigenetic research 5
a new Branch at Princeton
In memoriam 6
University dedicated to the
José Baselga 6
study of cancer metabolism. You can read all about it in
Sir Derek Roberts 6
here. Ludwig scientists at all the other locations have, Angelika Amon 7
meanwhile, given us much else to cover. You’ll read Pierre Languetin 7
about how targeting certain gut bacteria might boost
the efficacy of radiotherapy, how a common nutritional Events 8
supplement could restore the activity of exhausted anti- Virtual conference:
LUDWIG LINK | APRIL 2021
Exercise and cancer prevention 8
cancer T cells in tumors—and much, much more.
News roundup 9
You’ll also see in here a brief report on an engaging virtual Immune revival 9
Cancer Prevention and Physical Activity Conference Gut reaction 10
Ludwig convened in February in partnership with Cancer TAPS and more 10
Research UK and with support from the Conrad N. Hilton Stop signal 11
Foundation. The conference was one of several events Target: TNBC 11
planned this year to celebrate Ludwig’s 50th anniversary. The immunologic X-factor 12
Fuel gauge 12
An essential inefficiency 13
On a sadder note, we share the loss of four friends
Shattered sources 13
of Ludwig—former Ludwig Institute Board members
Structural solution 14
Sir Derek Roberts and Pierre Languetin, Ludwig MIT Liquid crystal dysfunctions 14
investigator Angelika Amon and former Scientific Advisor Tired TIL recharge 15
José Baselga. Personal nanovaccine 15
Rescued from ROS 16
The interview in this issue is with Ludwig Lausanne’s Lana Direct-on predictions 16
Kandalaft. And we asked Ludwig scientists to tell us how Carts of mice 17
the pandemic changed their perspective on balancing
Clinical trials 17
work and personal life. See some select responses in our Going viral 17
“Ask a scientist” section.
Q&A with Lana Kandalaft 18
Happy reading!
Ask a scientist 23
Rachel Reinhardt Required reading 25
Senior Vice President for Communications
3
Breaking news
A 50th ANNIVERSARY SPLASH
Ludwig Cancer Research announced on Altered metabolism is a salient feature The Ludwig Princeton team:
its 50th anniversary the newest Branch of cancer biology, as cancer cells
Kim Sokoloff
of the Ludwig Institute for Cancer must rewire their metabolic circuitry
Research. Based at Princeton University, to sustain their proliferation. Such
the Ludwig Princeton Branch will be adaptations not only drive tumor growth,
wholly dedicated to the study of cancer but cripple the anti-tumor immune
metabolism and the clinical translation response and compromise cancer
of its findings, which will be conducted immunotherapy as well. Metabolic
in partnership with RWJBarnabas Health dysfunction also causes the wasting
and Rutgers Cancer Institute of New disorder known as cachexia that
Jersey and other institutions. contributes enormously to cancer-
related mortality. Yet the metabolic Joshua Rabinowitz
“A more sophisticated understanding of rewiring comes at a cost to cancer cells:
John O’Boyle
cancer metabolism holds considerable it creates biochemical vulnerabilities
LUDWIG LINK | APRIL 2021
promise for the optimization of cancer that can be exploited for cancer
prevention and therapy, yet few prevention and therapy.
organizations have assembled a critical
mass of experts dedicated exclusively to The Ludwig Princeton Branch will
this promising frontier of research,” said focus on three main areas of cancer
Chi Van Dang, scientific director of the metabolism: metabolic interactions
Ludwig Institute for Cancer Research. between the tumor and the rest of the
“The Ludwig Princeton Branch will fill body, including how the body supports
that gap.” tumor growth and metastasis, and Eileen White
how tumors induce cachexia; dietary
Kim Sokoloff
Ludwig Princeton is directed by strategies for the prevention and
Princeton University’s Joshua treatment of cancer; and the interplay
Rabinowitz, and two other scientists of host metabolism, the gut microbiome
have been named founding Members of and the anti-cancer immune response.
the Branch: Associate Director Eileen
White, of Rutgers University and Yibin “Every one of us chooses, day-by-day,
Kang, also of Princeton University. what to eat,” said Ludwig Princeton
Branch Director Josh Rabinowitz.
“This new partnership goes to the heart “These choices don’t just impact
of what Princeton is all about. It draws metabolic health, but also immunity and Yibin Kang
on Princeton’s breadth of excellence cancer risk. We want to understand the
in fundamental research to drive real- underlying biochemical mechanisms and
world breakthroughs at the cutting apply this knowledge to find new ways to
edge of cancer care,” said Princeton prevent and treat cancer.”
University Provost Deborah Prentice.
4
Awards and distinctions
FOR ENDURING CONTRIBUTIONS
In November, Ludwig Lausanne received a conducted groundbreaking research
Team Science Award from the Society for on individualized immunotherapies—
Immunotherapy of Cancer for landmark such as dendritic cell vaccines and
research in basic and tumor immunology. the engineering and reinfusion of
The award recognizes research teams T cells for cancer therapy. Ludwig
around the world that have made lasting Lausanne scientists have made
contributions to the field of cancer significant discoveries on the immune
immunotherapy. Established in 1973 microenvironment of brain and ovarian
under the leadership of the immunologist tumors, the identification of potent
Jean-Charles Cerottini, the Lausanne patient-specific neoantigens for use
Branch initially led pioneering studies in novel immunotherapies and the George Coukos
on the development and functional mechanisms by which cancer metabolism Ludwig Lausanne
diversification of the immune system’s thwarts the immune response. Several
T cells, the underlying mechanisms and Ludwig researchers and alumni were also
LUDWIG LINK | APRIL 2021
dynamics of their responses and their recognized as members of other teams
recruitment for cancer immunotherapy. that received Team Science Awards,
The Branch today, directed by George including one led by former Ludwig CEO
Coukos, continues that tradition. It has and Scientific Director Lloyd Old.
FOR EPIGENETIC RESEARCH
Stephen Baylin, the Virginia and D.K. field and has led the development of
Ludwig Professor at Johns Hopkins biomarkers for cancer diagnostics and
School of Medicine, has been elected novel strategies that target epigenetic
Fellow of the American Association for mechanisms for the treatment of
the Advancement of Science. He was cancer. Stephen recently joined
recognized for his work on the influence Ludwig Oxford as a visiting professor
of epigenetic modifications—chemical of cancer epigenetics, where he will
“marks” made on DNA and its protein advise the Branch on its research in
scaffolding—on gene expression and cancer epigenetics and help guide its
cancer progression. More than 30 years collaborations in that area. He has also
ago, Stephen co-discovered cancer- been elected to the American Association Stephen Baylin
specific changes in the distribution of Physicians and is a member of the Ludwig Johns Hopkins
of DNA methylation that aberrantly National Academy of Sciences and
silence genes in cancer cells. He has co-leader of a Stand Up To Cancer
since remained at the forefront of the Dream Team for epigenetic therapy.
5
In memoriam
JOSÉ BASELGA
Former Scientific Advisor José Baselga, cancer treatments, particularly against
who helped guide the Ludwig Institute’s breast cancer. He was also known for
scientific strategy and staffing for his contributions to our understanding
ten years before leaving the Scientific of how dysregulation of the PI3K
Advisory Committee in 2016, died March signaling pathway drives the genesis
22nd from Creutzfeldt-Jakob disease, of cancers, and the translation of that
a rare, degenerative brain disorder. understanding into cancer therapies.
He was 61. At the time of his death, He was a Fellow of the American
José was executive vice president of Association for Cancer Research and a
oncology research and development for former President of the organization. He
AstraZeneca. José was renowned for his is survived by his wife Silvia and his four
work in developing and testing targeted children.
LUDWIG LINK | APRIL 2021
SIR DEREK ROBERTS
Former Ludwig Institute Board Member in industrial scientific research, first
Sir Derek Roberts passed away on at Plessy—one of Britain’s largest
February 17th, one month shy of his 89th electronics manufacturers—developing
birthday, due to complications from complex integrated circuits, and
COVID-19. He served on the Board for subsequently, heading up General
nearly 14 years before stepping down in Electric’s research activities. Elected
2012. An engineer who was twice provost a Fellow of the Royal Society and of the
of University College London, Sir Derek Royal Academy of Engineering in 1980,
Photo courtesy the Roberts family
oversaw several successful projects he was awarded a Commander of the
and the university’s expansion during British Empire in 1988 and knighted in
his tenure, including its merger with 1995 for services to engineering and
the Institute of Child Health. He was an education. The following year, he was
early pioneer of silicon-based integrated elected president of the British Science
circuit technology, now ubiquitous in Association. Read an interview with Sir
electronic devices from PCs to satellites. Derek in the November 2012 issue of
His professional life was spent primarily Ludwig Link.
6
In memoriam
ANGELIKA AMON
Ludwig MIT investigator Angelika Amon the world,” she said. “It’s like Christmas
passed away in October from ovarian when you were five. The beauty of
cancer. A prolific scientist, Angelika experimental science is that these
pioneered research on the underlying eureka moments are often shared with
mechanisms and consequences of other scientists, and I’m privileged to
chromosomal abnormalities, such as have experienced this.” Angelika was
aneuploidy, on fundamental processes a member of the National Academy of
of cellular life and demonstrated how Sciences, the American Academy of
those dysfunctions contribute to Arts and Sciences and the European
developmental disorders and cancer. Molecular Biology Organization. She
Other studies in her laboratory yielded was also a professor of Biology at
insights into the relationship between MIT, Member of the Koch Institute for
stem cell size, function and tissue aging. Integrative Cancer Research, and was
Angelika described what she loved most recently named Co-director of the Alana
LUDWIG LINK | APRIL 2021
about science in 2019, when accepting Down Syndrome Center at MIT. Click here
the Breakthrough Prize in Life Science. for a short video of Angelika speaking
“Making a discovery is the best feeling in about her work.
PIERRE LANGUETIN
Pierre Languetin, a former Ludwig for Economic Cooperation and
Board Member, passed away in October. Development and the European Free
A Swiss diplomat and central banker, Trade Organization. In 1976, he began
he joined the Board of Directors of the a decade-long stretch as a member
Ludwig Institute for Cancer Research of the governing Board of the Swiss
in 1987 and served with distinction for National Bank, and was named
two decades. Pierre was born on April chairman of its Executive Board in
30, 1923, in Lausanne and was educated 1985. In addition to his service to the
at the University of Lausanne and the Ludwig Institute, Pierre also served on
London School of Economics. A former the boards of numerous organizations,
trade negotiator, he often represented including Sandoz, Paribas Suisse and
Switzerland at the Organization the Swiss Reinsurance Company.
7
Events
VIRTUAL CONFERENCE:
EXERCISE AND CANCER PREVENTION
When Ludwig Cancer Research and the Conrad N. Others discussed technical issues in clinical studies of
Hilton Foundation launched a $10 million Cancer exercise and cancer. Kirsten Rennie of the University
Prevention Initiative in 2015, among their stated of Cambridge, for example, stressed the importance
goals was the promotion of cancer prevention in the of measuring physical activity independently in free
scientific and medical community, and support for its living, pointing to huge differences between self-
incorporation into public policy. A Cancer Prevention reports and objective measures of exercise among
and Nutrition Conference, convened in London in prostate cancer survivors. On the matter of behavioral
partnership with Cancer Research UK in 2018, along interventions, Wendy Wood of the University of
with a publication that emerged from the meeting, was Southern California argued that activities reinforced by
a first step in that direction. The second was taken rewards—even just “fun”—are more likely to establish
from February 23rd to 25th, 2021, in an international, healthful habits, and discussed why habit, more than
virtual Cancer Prevention – Physical Activity rationale, might sustain healthful behaviors.
Conference organized by the same partnership.
LUDWIG LINK | APRIL 2021
On the final day, a fascinating session covered the role
After opening remarks by Scientific Director Chi Van of the built environment in medical outcomes, with
Dang and Ludwig Oxford’s Peter Ratcliffe, speakers speakers pointing out how little health considerations
covered the existing epidemiology on physical factor into urban planning decisions. In one particularly
exercise and cancer, followed by a session on the engaging talk, Rich Mitchell of the University of
molecular and physiological mechanisms that might Glasgow discussed his studies examining how poverty
drive such effects. In the latter session, Ludwig and the built environment interact with such things as
Harvard investigator Rakesh Jain discussed his lab’s childhood activities and transportation to expose kids
discovery that exercise normalizes the vasculature of to certain foods, tobacco and other factors with lasting
the tumor, improves anti-cancer immune responses consequences for health.
and reduces metastasis in mouse models. Memorial
Sloan Kettering’s Lee Jones, meanwhile, presented In a concluding Big Ideas session of the conference,
his preclinical studies on the significant benefit of Chi noted the pressing need to figure out the
exercise on slowing progression of certain types of mechanistic basis of exercise effects on the
breast cancer. pathophysiology of cancer. He raised the intriguing
possibility that a mechanistic understanding could
The second day covered clinical studies of also lead to pharmacological interventions with
physical exercise in cancer outcomes and those of matching effects for patients who can’t exercise due
interventions that seek to instill healthier behaviors. to their condition. A poll conducted during this session
One speaker, Robert Newton of Edith Cowan University, suggested most attendees agreed that mechanistic
presented an ongoing study showing that changes in studies are the order of the day. This should help guide
immune factors induced by exercise might slow growth the research agenda of the field.
of prostate cancer cells even when men are resting.
8
News roundup
Taha Merghoub Sadna Budhu Jedd Wolchok
Ludwig MSK Ludwig MSK Ludwig MSK
IMMUNE REVIVAL
LUDWIG LINK | APRIL 2021
Phosphatidylserine (PS) is a small effect was accompanied by an increase
molecule mainly found at high levels in the proportion of pro-inflammatory
on the outer membrane of dying cells, macrophages and an increase in the
from where it is known to promote an recruitment and activation of T cells in
immunosuppressive microenvironment tumors. Adding anti-PD-1 checkpoint
in tumors through its interaction with blockade immunotherapy to the mix
its receptors. A study led by Ludwig further enhanced T cell activation,
MSK researchers Taha Merghoub, Sadna responses to radiotherapy and survival
Budhu and Jedd Wolchok published in of the mice. The researchers also
Cell Reports in January found expression showed that immune cells in the blood of
of PS on live tumor-infiltrating immune melanoma patients who have received
cells rises after a single dose of radiation radiotherapy similarly express higher
delivered to melanoma tumors in levels of PS. These findings suggest
mice. The researchers found that PS- that patients could benefit from the
blockade with the antibody mch1N11 concurrent blockade of PS and PD-1 in
enhanced the effects of radiotherapy combination with radiotherapy.
and extended survival of the mice. The
9
News roundup
GUT REACTION
In a study published in the Journal of by Ralph and Yang-Xin have shown that
Experimental Medicine in January, Ludwig radiation activates a signaling pathway in
Chicago Co-director Ralph Weichselbaum dendritic cells that primes other immune
and Yang-Xin Fu of the University of Texas cells—killer T cells—to attack tumors. This
Southwestern Medical Center showed pathway, controlled by a protein named
how certain gut bacteria can reduce the STING, ramps up the dendritic cells’
efficacy of radiotherapy. They identified production of immune-stimulating factors
two families of bugs—Lachnospiraceae known as type-1 interferons (IFN-I), which
and Ruminococcaceae—that interfere boost T cell activation. In this study, they
with radiotherapy in mice and described show that butyrate inhibits a step of the
how the short-chain fatty acid butyrate, biochemical signaling cascade that links Ralph Weichselbaum
a metabolic byproduct of these bacteria, STING activation to the production of Ludwig Chicago
undermines the therapy. The antibiotic IFN-I. The researchers suggest that the
vancomycin decreased the abundance highly selective targeting of butyrate-
LUDWIG LINK | APRIL 2021
of butyrate-producing gut bacteria and producing gut microbiota may augment
enhanced antitumor responses following the radiotherapy sensitivity of tumors and
radiotherapy in mice. Previous studies led improve patient responses.
TAPS AND MORE
Chemical, or epigenetic, modifications named TET-assisted pyridine borane
made to the DNA base cytosine play an sequencing (TAPS). Now the gold
important role in the regulation of gene standard of such technologies, TAPS
expression across the genome. The was at the heart of a biotech spin-
base is chemically modified with four off that was bought late last year by
chemically and functionally distinct Exact Sciences, which will use the
“marks”, with 5-methylcytosine (5mC) method in novel cancer diagnostics. In
being the most common and most January, researchers led by Chunxiao
frequently disordered in cancer. The and his University of Oxford colleague
others are 5-hydroxymethylcytosine Ahmed Ahmed reported in Nature
(5hmC), 5-formylcytosine (5-fC) and Communications an expanded toolkit for Chunxiao Song
5-carboxycytosine (5caC). The Ludwig the direct and quantitative sequencing Ludwig Oxford
Oxford laboratory of Chunxiao Song of all four cytosine epigenetic marks—a
reported in 2019 a sensitive, cost- new version of TAPS for 5mC (named
effective and efficient method for the TAPSβ) and brand new methods for the
whole-genome sequencing of 5mC other three.
10News roundup
STOP SIGNAL TARGET: TNBC
During cell division, protein cables Triple negative breast cancers (TNBC)
called microtubules latch on to a copy bearing mutations to their BRCA genes
of every chromosome at a structure can be treated with a class of drugs known
called the kinetochore and pull one of as PARP inhibitors, but the benefits of this
each to opposite poles of the dividing therapy are often fleeting. Since PARP
cell. In healthy cells, this choreographed inhibitors can also help stimulate anti-
segregation of chromosomes is tumor immune responses, researchers
monitored by a “spindle checkpoint” that are already examining their combination
halts cell division if even one kinetochore Arshad Desai with immunotherapy to improve
is not firmly attached to a microtubule, Ludwig San Diego outcomes. In a December paper in Nature
ensuring that chromosomes are equally Cancer, a team led by Ludwig Harvard
distributed to each daughter cell. In investigator Jennifer Guerriero exposed
a January paper in Science, Ludwig a potential challenge to such strategies—
San Diego’s Arshad Desai, Pablo Lara- and offered a possible solution. PARP
LUDWIG LINK | APRIL 2021
Gonzalez and colleagues detailed the inhibitors, the researchers showed, can
mechanism by which the checkpoint also promote an immune-suppressive
is generated by the association of two tumor microenvironment (TME), pushing
proteins, Cdc20 and Mad2. Using a visual immune cells known as macrophages in
probe that tracks one of the proteins, the TME into an immunosuppressive state
the team detailed how Cdc20 and Mad2 through the reprogramming of their lipid
are geometrically constrained at the metabolism. These immunosuppressive
kinetochore, held in a particular position Pablo Lara-Gonzalez macrophages express high levels of the
by phosphorylation events that prime Ludwig San Diego CSF-1 receptor, which is essential to their
their interaction, and how their enzymatic survival. Jennifer and her colleagues
substrates are locally delivered to them demonstrated that treating mice bearing
to generate the wait signal. The findings BRCA-deficient TNBC tumors with a
help explain why that signal is generated combination of PARP inhibitors and
at kinetochores and not elsewhere CSF-1R blocking antibodies extended
in the cell, thereby ensuring that no survival of the animals. The effect
chromosome is left behind. was mediated primarily by activation
of cancer-targeting killer T cells in the
less immunosuppressive TME. The
authors suggest that combining PARP
inhibition with CSF-1R inhibition could be a
Jennifer Guerriero promising therapeutic strategy for BRCA-
Ludwig Harvard deficient TNBCs.
11News roundup
THE IMMUNOLOGIC FUEL GAUGE
X-FACTOR
Sick animals often lose their appetites.
Though this behavior is widely observed
The liver X receptor β (LXRβ) is a nuclear across species, its consequences on the
receptor that plays a key role in the effector T cells battling infection was
regulation of lipid and cholesterol not clear. In a December paper in the
metabolism and inflammatory immune Proceedings of the National Academy of
responses. Yet its precise role in T cell Sciences, Ludwig MSK Director Alexander
biology has thus far been unclear. In a Rudensky and colleagues showed that
December Brief Definitive Report in the Alexander Rudensky starvation during infection decreases
Journal of Experimental Medicine, a team Ludwig MSK the number of effector T cells in mice
led by Ludwig MSK’s Alexander Rudensky through mechanisms governed by the
and Clarissa Campbell revealed that the cells’ Farnesoid X Receptor (FXR), a
loss of LXRβ in a mouse model leads to a nuclear receptor also involved in liver
severe deficiency of T cells accompanied responses to fasting and refeeding. That
LUDWIG LINK | APRIL 2021
by the spontaneous activation of effector loss of effector T cells, they showed,
T cells. Studies of chimeric mice with could be reversed by the provision of the
mixed populations of LXRβ-deficient T sugar glucose, supporting the sugar’s
cells and normal T cells showed that the availability as a determinant of effector
receptor is needed for T cell fitness, and T cell survival. Deletion of FXR in T cells
that its loss especially compromises prevented their loss during starvation,
regulatory T cells (Tregs), which suppress altered their utilization of fuel from
effector T cells and protect tumors from Clarissa Campbell glucose to other nutrients and improved
anti-cancer immune responses. LXRβ Ludwig MSK their fitness. It also caused weight loss
deficiency, Alexander and his colleagues in the mice. The study, supported by
show, profoundly compromises Treg the Ludwig-Hilton Cancer Prevention
function. Indeed, the loss of just one Initiative, identified a mechanism by
copy of the LXRβ gene in Tregs suffices which the host scales immune responses
to induce early and fatal autoimmune in reaction to nutrient availability, and
disease in mice. The researchers argue showed that FXR is the sensor in T cells
these findings suggest the receptor that triggers those responses.
could be a prime target for immunological
therapies.
12News roundup
AN ESSENTIAL SHATTERED SOURCES
INEFFICIENCY
Circles of DNA unassociated with
Cancer cells burn sugar using an chromosomes, extrachromosomal
inefficient metabolic pathway known as DNAs (ecDNA) encode multiple copies
fermentation, which captures much less of cancer genes and drive tumor
energy as ATP and which most healthy evolution, growth and drug resistance.
cells—except rapidly proliferating ones, Identifying where ecDNA comes from
like activated T cells of the immune has been an important challenge of
system—use mainly when starved of cancer research. In December, a team
oxygen. A study led by Ludwig MIT’s Matthew Vander Heiden led by Ludwig San Diego’s Don Cleveland
Matthew Vander Heiden and published Ludwig MIT and Peter Campbell of the Sanger
in December in Molecular Cell examined Center reported in Nature that ecDNAs
why this is the case. Matthew and his are formed by chromothripsis—or the
colleagues show that fermentation, or shattering and shuffled reassembly
aerobic glycolysis, helps cells regenerate of chromosomes. While earlier work
LUDWIG LINK | APRIL 2021
large quantities of NAD+, a chemical led by Don and Peter had established
essential to the synthesis of some large that chromothripsis of missegregated
molecules like DNA that all cells need chromosomes can produce the complex
to divide. Inhibiting fermentation and genome rearrangements found in many
forcing cancer cells to make ATP, the tumors, the researchers now report that
currency of cellular energy, through chromothripsis drives the evolution of
aerobic respiration slowed their growth. gene amplification in cancer through
When those cells were then additionally Don Cleveland production of ecDNA, including the
treated with a drug that stimulates NAD+ Ludwig San Diego induction of drug resistance through
regeneration, however, their proliferative the generation of ecDNAs carrying a
frenzy was restored. Cancer cells, it gene that inactivates an anticancer
appears, need NAD+ more than they drug. They showed that once formed,
do ATP. When ATP abounds, aerobic ecDNA undergoes successive rounds
respiration slows down, and so does of chromothripsis to spawn additional
mitochondrial NAD+ regeneration. rearranged ecDNAs that drive increased
Cancer cells and activated T cells, the drug resistance by further amplification
researchers demonstrate, maintain high of genes responsible for the resistance.
levels of NAD+ by employing the less The study lays the groundwork for
efficient generator of ATP: fermentation. combination therapy in which a
The findings suggest drugs that force chemotherapeutic drug is paired with
cancer cells into aerobic respiration or another drug that prevents the DNA
inhibit NAD+ production could be useful as fragments created by chromosomal
cancer therapies. shattering from closing to form ecDNA
circles.
13News roundup
STRUCTURAL SOLUTION
The poison arsenic is a well-worn device of to the large variety of p53 mutations,
crime novels. But in low doses it can also be their diverse effects and a lack of
a useful treatment for acute promyelocytic sites on the p53 protein that can be
leukemia. Building on the latter theme, a easily targeted by drugs. However,
study led by Ludwig Oxford Director Xin over half of all p53 mutations cause
Lu and Min Lu of the Shanghai Institute of structural alterations that affect
Hematology performed a screen for drugs p53 activity. These mutants were
that could reactivate mutant forms of the the focus of the study reported in
p53 tumor suppressor and found that arsenic Cancer Cell in December. For some
compounds—including arsenic trioxide— of the structural mutations, arsenic
rescued some structural defects in p53. trioxide was also able to reactivate Xin Lu
Although p53, called the “guardian of the the tumor suppressor function of Ludwig Oxford
genome,” is the most frequently mutated p53 in experimental models. It is now
gene in human cancer, efforts to devise being tested in a phase I clinical trial
LUDWIG LINK | APRIL 2021
drugs that reactivate the mutated protein in patients with p53-mutated blood
have generally come up short. This is due cancers.
LIQUID CRYSTAL DYSFUNCTIONS
Loss of function of the RNA-binding protein cores. In animal studies, inhibiting the
TDP-43 is seen in neurodegenerative proteasome—which degrades proteins—
diseases, such as ALS, Huntington’s within neurons to mimic the aging-related
disease and Alzheimer’s disease. A study decline in its activity induced the formation
led by Ludwig San Diego’s Don Cleveland of TDP-43-containing spherical shells. The
reported online in Science in December that shells convert into aggregates when ATP
RNA-binding deficient TDP-43—which is levels drop. These findings suggest the TDP-
produced by neurodegeneration-causing 43 aggregation seen in neurodegenerative
mutations or biochemical modifications to diseases may have its origins in anisosomes.
the protein—drives TDP-43 de-mixing into The study also explains the peripheral
liquid spherical shells with liquid cores in the neuropathy caused by bortezomib, a Don Cleveland
nuclei of neurons. Don and his colleagues proteasome inhibitor used to treat multiple Ludwig San Diego
named these structures anisosomes and myeloma. The researchers showed that
identified the major components of the anisosomes form in sensory neurons in
liquid core to be HSP70 family chaperones, bortezomib-treated mice and rats and are
whose activity, powered by the molecule thus likely to form in multiple myeloma
ATP, maintains the liquidity of shells and patients who develop peripheral neuropathy.
14News roundup
TIRED TIL RECHARGE PERSONAL
NANOVACCINE
Ludwig Lausanne’s Ping-Chih Ho and his
colleagues reported in Nature Immunology Ludwig Chicago investigator Wenbin Lin
in October a novel mechanism by which and his colleagues reported in Science
the harsh microenvironment of the Advances in October their design and
tumor enervates tumor-infiltrating T preclinical evaluation of a combined
lymphocytes (TILs). They also showed nanotechnology-based radiotherapy
that a common nutritional supplement, strategy that effectively generates a
nicotinamide riboside (NR), could personalized cancer vaccine within the
revive the anti-tumor activity of the Ping-Chih Ho body. It revolves around nanoparticles
TILs. Starved of oxygen and essential Ludwig Lausanne named nanoscale metal-organic
nutrients in tumors, TILs adjust metabolic frameworks (nMOFs) developed in
processes to compensate, in part by Wenbin’s lab that amplify the cell-killing
making more mitochondria (the energy free radicals generated by radiotherapy,
generators of the cell). Meanwhile, boosting its effects. Wenbin’s team
LUDWIG LINK | APRIL 2021
prolonged and fruitless stimulation by adapted their nMOFs to carry an adjuvant,
cancer antigens pushes TILs into an a substance that stimulates vaccine-
exhausted state. Ping-Chih and his team induced immune responses. The adjuvant,
found that exhausted TILs are packed known as a CpG oligonucleotide, drives
with dysfunctional mitochondria, mainly the maturation of the immune system’s
because the TILs can’t remove damaged dendritic cells, which activate and direct
ones. This, they showed, is a cause, not a cytotoxic T cells toward cancer cells.
consequence, of exhaustion. NR has been Wenbin Lin In mouse models of pancreatic and
shown by Ludwig Lausanne researchers Ludwig Chicago colon tumors, which tend to harbor few
and others to improve mitochondrial viable cytotoxic T cells and so resist
fitness, so Ping-Chih and his colleagues immunotherapy, irradiating tumors
examined whether it might rescue TILs treated with the nMOFs caused a release
from terminal exhaustion. Their cell of the CpG adjuvant and the shedding of
culture experiments showed that NR cancer antigens and molecular danger
improved the mitochondrial fitness signals by dying cells. This drove dendritic
and function of T cells in conditions cell maturation and activation, which
resembling those of the tumor. More stimulated anti-tumor T cells and caused
notably, dietary supplementation with regression of treated tumors. When
NR stimulated the anti-tumor activity combined with anti-PD-L1 checkpoint
of TILs in mouse models of melanoma blockade immunotherapy, the treatment
and colon cancer. When combined with elicited immune responses against
checkpoint blockade immunotherapies, it untreated tumors as well—and an 83%
also significantly inhibited the growth of cure rate in mice implanted with the
tumors in the mice. immunosuppressive colon cancer.
15News roundup
RESCUED FROM ROS DIRECT-ON PREDICTIONS
Cancer-associated mutations are known Immune checkpoint inhibitors like anti-
to stabilize the transcription factor, PD-1 antibodies improve survival in
NRF2, that controls the expression of advanced non-small cell lung cancer
genes involved in cellular antioxidant (NSCLC). However, conventional imaging
defense systems, which shield DNA often can’t identify which patients treated
and other vital molecules from highly with these agents will benefit from such
reactive molecules called reactive oxygen therapy. In a Cell paper published in
species (ROS). In a Molecular Cell paper October, a team led by Ludwig Stanford’s
published in October, Ludwig Harvard Joan Brugge Ash Alizadeh and Maximilian Diehn and
Co-director Joan Brugge and colleagues Ludwig Harvard Matthew Hellmann of Memorial Sloan
reported their analysis of how NRF2 Kettering Cancer Center reported a
contributes to cancer cell growth and method to accurately predict early in
survival in experiments using lung cancer treatment which patients with NSCLC
spheroid models—cultured, three- are likely to benefit from PD-1 checkpoint
LUDWIG LINK | APRIL 2021
dimensional mimics of tumors. Their blockade. Called DIREct-On, (for Durable
studies showed that its hyperactivation Immunotherapy Response Estimation
is required for both proliferation and by immune profiling and ctDNA-On
survival of spheroid cultures, though treatment), the method incorporates
distinct signaling pathways control each three types of biomarkers to predict
outcome. A pathway mediated by mTOR treatment responses: the level of
supports proliferation. As for survival, mutation in tumors, changes in levels
NRF2 activity protects cancer cells Ash Alizadeh of circulating tumor DNA (ctDNA) and
within the spheroid that are deprived Ludwig Stanford levels of circulating cytotoxic T cells.
of contact with the extracellular matrix DIREct-On benefits from the noninvasive
from a type of programmed cell death measurement of biomarkers not only
known as ferroptosis, which is mediated before but during treatment as well.
by ROS. But when cells lack NRF2, a In preliminary studies, it accurately
critical suppressor of ferroptosis, GPX4, predicted progression-free survival
and related proteins are expressed at from blood samples collected after one
high levels. Joan and her team show that treatment cycle and was more precise
inhibiting both NRF2 and GPX4 leads to than use of any of the three variables
the death of cancer spheroids. The results alone. Combining all three resulted in
reveal a vulnerability in tumors dependent the prediction of durable clinical benefit
on NRF2 hyperactivation that might be with a sensitivity of 94% and specificity
targeted for the development of novel Maximilian Diehn of 89%. DIREct-On could help physicians
cancer therapies. Ludwig Stanford quickly determine whether anti-PD-1
immunotherapy should be continued,
modified or stopped.
16News roundup Clinical trials
CARTS OF MICE GOING VIRAL
Chimeric antigen-receptor (CAR)-T Targovax, a company developing
cell therapy involves taking a patient’s immune activators for combination
peripheral blood T cells and engineering therapy in solid tumors, completed
them with a receptor that redirects part 1 of its two-part, open label phase
them to attack their tumor. Though such 1 trial evaluating the combination of
therapies have been approved for blood the oncolytic virus ONCOS-102 and the
cancers, their application to solid tumors checkpoint blockade durvalumab, a PD-
has proved challenging, in part because L1 inhibitor, for colorectal cancer (CRC)
the microenvironments of solid tumors Melita Irving and platinum-resistant ovarian cancer
suppress immune responses. Meanwhile, Ludwig Lausanne that has spread to the peritoneum—the
due to technical difficulties associated membrane that lines the inner wall of the
with developing mouse CAR-T cells, abdomen. ONCOS-102 is an experimental
new CAR therapies have typically been cancer therapy comprised of an
preclinically evaluated using human CAR-T engineered adenovirus that replicates
LUDWIG LINK | APRIL 2021
cells in mice that lack an immune system. specifically inside cancer cells, leaving
The CAR-T cells are thus not challenged healthy cells unharmed. The trial met
in the context of inhibitory immune the pre-defined efficacy threshold
infiltrates in tumors. In November, Ludwig in the CRC cohort at week 24 and the
Lausanne’s Melita Irving, George Coukos, second part of the CRC expansion
Evripidis Lanitis and colleagues reported cohort is now open for recruitment. The
in the Journal of Experimental Medicine treatment did not meet that threshold
a method to overcome that difficulty George Coukos for the ovarian cancer cohort, which
involving, among other things, the Ludwig Lausanne is now closed. The trial was designed
sequential use of three immune factors with a dose-escalation phase assessing
known as interleukins (IL-2, 7 and 15) in three different dosing levels, followed
the cultivation of mouse CAR-T cells. The by an expansion phase. The study
team also developed “4th generation” (4G) is sponsored by Ludwig and led by
CAR-T cells engineered to co-express Ludwig MSK’s Dmitriy Zamarin. CRC is
the IL-15 protein, which stimulates T cell a challenging disease to treat, with a
proliferation and survival, and showed response rate to immune checkpoint
that their CAR-T cells were superior in inhibitor monotherapy of less than 5%.
persistence, fitness and efficacy in a The researchers are betting immune
mouse model of melanoma. Notably, the activation by ONCOS-102 will sensitize
4G CAR-T cells reprogramed the tumor these tumors to immune checkpoint
microenvironment by activating tumor- Evripidis Lanitis inhibition and improve the response
targeting natural killer cells and causing Ludwig Lausanne rate.
a decline in M2 macrophages that can
suppress anti-cancer responses.
17Q&A
LANA
KANDALAFT
ASSOCIATE DIRECTOR
OF CLINICAL TRANSLATION,
LUDWIG LAUSANNE
Can you tell us about what excites you
most in your work right now?
We’re pretty unique here at the Ludwig
Lausanne Branch, in that there are not
many translational programs around the
world like ours. I have an amazing team to
LUDWIG LINK | APRIL 2021
work with in developing cancer vaccines
and other immunotherapy products for
our patients. And right now, we are in
an excellent position to deliver some
innovative products to them. Our work is
very gratifying because we are able to see
our technologies being implemented in
clinical protocols and witness first-hand
how a treatment is working and whether it
is benefitting an individual patient.
You’ve done a lot of research on
ovarian cancer. How optimistic are
you about near-term opportunities for
immunotherapy treatments for this kind
of cancer?
While we don’t have immunotherapy for better response. Chemotherapy and PARP
ovarian cancer as yet, we have a lot of inhibitors are viable combination partners
promising leads. I think the challenge is for immunotherapy and combining
going to be defining exactly which patients checkpoint inhibition with other drugs
may get the best results from different may lead to some new options for
approaches. There are a couple of studies patients. But none of these combinations
out whose results are encouraging and are standard of care right now. Now
indicate we need combination therapies the more that we understand the tumor
along with chemotherapy to produce a microenvironment and its influence on a
18Q&A
handle. Number two, in order to ramp
up production, you have to have the
infrastructure to actually manufacture
It’s a different ballgame when you interact with these products. Producing them and
getting them to patients is complex
patients and their husbands or mothers or sisters ...
and very challenging. While it took us
part of my attachment to ovarian cancer stems quite a few years to build, the Center of
Experimental Therapeutics (CTE) has
from my personal experience with patients. two GMP manufacturing facilities: the
Tumor Processing Facility and the Cellular
Manufacturing Facility. Just as CAR T-cell
therapy has been approved for standard
of care for some cancers, I believe these
patient’s response to therapy, the more new immunotherapies will be as well.
we’ll be able to understand how various And third, once we’ve developed these
combination therapies work and which therapies there are some big questions
LUDWIG LINK | APRIL 2021
ones might work best. to answer. How will the world adapt?
Will pharma make use of all the good
My interest is in vaccines, and I have a technology we’ve developed and run with
paper out right now with my colleagues it? Will every hospital in every country
here Alexandre Harari and Cheryl Chiang and in every city have the infrastructure
at the Ludwig Lausanne Branch on a in-house to treat its patients? Will these
personalized cancer vaccine strategy therapies eventually become part of the
that recognizes the importance of T cells standard of care? We have a lot of hurdles
for controlling ovarian cancer. Some to overcome, but I’m confident they are all
interesting early data have come out that doable.
may lead us in directions that we want
to go, but larger studies need to be done Given all these challenges, what is it
to validate the findings. Vaccines are about ovarian cancer that drives you?
not the cure, however. It’s my hope that It’s what’s called the silent killer because
they will eventually be integrated into the it’s a very tough cancer to detect and by
standard of care, but they will not be the the time a woman receives a diagnosis,
definitive cure for ovarian cancer. the disease is quite advanced, at either
Stage III or IV. I started working on it at the
What worries you the most about Ovarian Cancer Research Center at the
developing these therapies? University of Pennsylvania with George
First of all, they are difficult to develop, Coukos and found it very challenging to
and the difficulty is the technology— treat. The disease landscape is such that
choosing the right antigen, choosing the cancer bounces back in 85% of women
the right TCR (T cell receptor). The who undergo the standard of care, which is
T cells themselves are difficult to surgery followed by chemotherapy. I think
19Q&A
there is a watchful waiting period with this
disease where a vaccine could be given to
women in remission to prevent recurrence.
But it might have been my exposure to
patients when I was at Penn that changed
my mentality and the way I approach
this disease. It’s a different ballgame
when you interact with patients and their
husbands or mothers or sisters or other
close relatives. And I think part of my
attachment to ovarian cancer stems from
my personal experience with patients,
many of whom have become friends.
Can you tell us what you find most
LUDWIG LINK | APRIL 2021
Lana with Ludwig Lausanne’s Alexandre Harari, left, and Director George Coukos.
stimulating about the research
environment at Ludwig Lausanne?
At Ludwig we are really very lucky. The
leadership has set a specific direction operation focused on vaccines. It was
for the organization, and everyone on the difficult because we didn’t have a Good
team has a shared sense of purpose, and Manufacturing Practice (GMP) facility
we are all working towards one goal. Or, and had to outsource everything. Here
as I like to say, we’re all drumming to the in Lausanne, we built a department
same beat. Our focus is on translational that has it all. We’re one of the largest
science—primarily tumor immunology immunotherapy centers in Europe, and
and the design and development of we have it all right here—the researchers,
novel immunotherapies. I admit it can be the doctors and the patients. Within the
daunting in terms of career development CHUV’s Department of Oncology, we
because not every member can become created the CTE, which I run with a staff
their own PI or have their own lab or run of 140. We have a clinical investigation
their own Branch. But at the end of the unit to run our clinical trials and two
day, we’re all working on something that GMP manufacturing facilities for cancer
will eventually get to our patients and immunotherapies. Without these
hopefully make a difference. resources, we could not have achieved
what we are achieving right now.
What has it enabled you to do that you
could not do previously? Your training has been very international.
Prior to coming here, I worked with George What perspective does that provide for
at Penn developing immune therapies for you?
ovarian cancer patients. It was a small That you can be whoever you want to
20Q&A
I lack the time right now to even think
about using social media. I would need the
support of a very good communications
team to even start.
What would our readers be surprised to
know about you?
I’m aware that people perceive me as a
workaholic, and I know they think that
I have no private life. But I do. I am a
mother with two amazing boys. I’m a
very good cook and have even mastered
a Lebanese lamb dish that my dad said
was even better than my mother’s. Music
is a big part of my life. I wrote my entire
PhD thesis to Jon Bon Jovi’s music—
LUDWIG LINK | APRIL 2021
Lana with Ludwig Lausanne Director George Coukos. played very loud. And since moving to
Switzerland, I have fallen in love with the
mountains and ski touring. It’s my new
be wherever you are. It doesn’t matter passion. Exhausting, but so beautiful.
if you’re in India, Spain, the U.S. or
Switzerland. All it takes is the right Would you share a story that led to you
mindset and the right attitude. Every new choosing your field of work?
venue presents a different challenge. It was in Cardiff, Wales, where I was
Each institution has a lot to offer. You working on my PhD in pharmaceutical
have to adapt, as each has its own mission drug delivery. I had just started a course
and its own way of doing things. There in pharmaceutical biology that was
are new languages to learn, new cultures interesting, but I couldn’t see a real-world
to embrace and new techniques to learn. application. One evening when I was
But since I left home at such a young age, sitting at the bench next to my computer,
I was able to adapt quite easily and absorb I came across a paper written by Doug
everything around me like a sponge. And Hanahan and Bob Weinberg entitled The
bottom line, science is science, whether Hallmarks of Cancer. I said to myself, “Ah,
you are working in the U.S. or Switzerland. Lana, this is what you need to do. You need
to deliver drugs to cancer. This is what you
What is the most effective/best way for must do.” So I immediately started looking
scientists to use social media to engage, into postdoc opportunities at the National
communicate and interact? Cancer Institute in Bethesda. That was
Honestly, I don’t know. It’s very important a turning point in my life. When I came
to communicate about your work and to Lausanne in 2012, and first saw Doug
share it with others, but I have to admit Hanahan, I was so excited and thrilled to
21Q&A
actually meet him that I know my face
turned completely red. I kept saying to
myself, Doug Hanahan is here, and it was
his amazing paper that really touched me Since I left home at such a young age, I was able to
and changed my life.
adapt quite easily and absorb everything around me
When you’re not wearing your many like a sponge. And bottom line, science is science,
science hats, what other activities are
you involved in?
whether you are working in the U.S. or Switzerland.
I’m at a stage in my life where my role as
a mother has changed. I have a different
connection with my two sons, who are
now 10 and five years old, than I did when
they were younger. While I encourage
them to be independent, they will often matter whether you are male or female,
bike alongside me when I run. I still play everyone is working towards the same
LUDWIG LINK | APRIL 2021
a lot of tennis and in winter we ski a lot goal. Here at the CHUV, women are well
on the weekends. Opera is not my thing, represented as 69% of the employees
sports are. And I watch a lot of movies are female, and many are in leadership
with the boys and, of course, listen to positions.
music.
My role as a mentor is very important to
What kind of music do you listen to? me, and I often wish I had more time to
I’m into French rap because it’s what my devote to it. I am often approached by
kids are listening to, and I want to be cool. young women who want to know how I
I also listen to a lot of oldies because was able to achieve what I did, what my
growing up, my dad was always playing life is like, and ask whether a life outside
them. But it’s definitely the music from the lab possible. Mentoring the younger
the 80’s that gets me pumped up. It’s great generation is key to helping them reach
music to run to. the next level. I had one very talented
female postdoc who came to work for
There has been a lot of discussion in the me and over the years received a number
media lately about women in science. of promotions, and ultimately became
What has been your experience as a a key member in our department here
female scientist? How do you see your at the CHUV. She now works in the
role in helping to mentor women? pharmaceutical industry. One day, she
Again, I have been very lucky in that I have came to me and said, “Lana, you didn’t just
always worked in an environment where give me a job, you gave me a career.” That
the leadership has been nothing but touched me deeply and reinforced how
supportive of women. The field of science important it is to mentor and inspire the
is challenging as it is, and it doesn’t really next generation.
22Ask a scientist
How has the pandemic changed your perspective
on balancing your work and personal life?
Prior to the pandemic, I had a system and support structure that allowed me to
balance my work in the lab and the clinic with caring for and spending good time
with my husband and our four children. That system of balance disappeared
when the pandemic hit and schools shut down. My husband (who is also in
academic medicine) and I have been doing 100% work and 100% childcare
at the same time, all the time it seems. To cope with this new unbalanced
reality, I have been learning to say “no” more to work commitments, to reset
my expectations of what I can accomplish every day, and to seek and cherish
those rare quiet and un-interrupted moments when I can think creatively about
LUDWIG LINK | APRIL 2021
an experiment or write a paper. It has been hard. But the extra time with my
children and a chance to take a break from frequent academic travel has been
really wonderful, and my ability to multi-task has improved to a new level.
MICHELLE MONJE DEISSEROTH
Ludwig Stanford
Prior to the pandemic, research was the center of my life, and I had to
travel frequently for scientific meetings. I see now that my mindset was not
sustainable, especially on maintaining my personal life, as well as supporting
the development of my lab members. After the shocking experience and a
‘valuable’ reset happened in 2020, I realize that work-life balance is key to
sustaining my research motivation and appreciate the fact that everyone in
my lab is heading to our goal in their own way. Although this pandemic is sad in
many ways, I do feel that it brings positive changes for our research and training
culture.
PING-CHIH HO
Ludwig Lausanne
23Ask a scientist
This pandemic has brought a general sense of uncertainty and disorientation.
The possibility to go to conferences and build a good network is still missing,
and I fear this will have a negative impact on my career. However, I will do my
best and fight to keep my research and progress going even in this tough
period.
FRANCESCA ALFEI
Ludwig Lausanne
With hours limited by the shift system, I have found I am able
to achieve more than I expected by being more efficient, whilst
the extra time at home has highlighted the indispensable nature
of interests outside of work. I have also learned not to worry about
things that you have no control over.
LUDWIG LINK | APRIL 2021
MICHAEL McCLELLAN
Ludwig Oxford
For me, the pandemic has emphasized the importance of having firm
boundaries between work and personal time. Home-schooling whilst in a lab
meeting, responding to emails whilst shushing a crying baby, cramming in lab
time then rushing home for childcare, etc. This is not conducive either to good
research or to good parenting. In the future I will be very grateful to work and to
parent at separate times and with my full focus.
ALICE NEAL
Ludwig Oxford
I’ve realized that achieving a work-life balance is not just a worthwhile goal—
it is vital for mental and physical health and future success. I’ve learned that
mastery of work-life balance comes down to how well we can prioritize the
aspects of our lives that we most enjoy, whether professional or personal.
SEAN PITRODA
Ludwig Chicago
24Required reading
Cancer Cell
Ludwig Chicago Ludwig Lausanne Ludwig MSK
2020 December 7
Journal of Journal of Cell Reports Online ahead of print
Experimental Medicine Experimental Medicine 2021 January 12
Arsenic Trioxide Rescues
2021 January 26 2020 November 6 Targeting phosphatidylserine Structural p53 Mutations
Suppression of local type I Optimized gene engineering enhances the anti-tumor through a Cryptic Allosteric Site.
interferon by gut microbiota- of murine CAR-T cells reveals response to tumor-directed
Chen S, Wu JL, Liang Y, Tang YG,
derived butyrate impairs the beneficial effects of IL-15 radiation therapy in a preclinical
Song HX, Wu LL, Xing YF, Yan N,
antitumor effects of ionizing coexpression. model of melanoma.
Li YT, Wang ZY, Xiao SJ, Lu X,
radiation. Lanitis E, Rota G, Kosti P, Ronet C, Budhu S, Giese R, Gupta A, Chen SJ, Lu M.
Yang K, Hou Y, Zhang Y, Liang Spill A, Seijo B, Romero P, Dangaj Fitzgerald K, Zappasodi R, Schad
H, Sharma A, Zheng W, Wang L, D, Coukos G, Irving M. S, Hirschhorn D, Campesato LF,
Torres R, Tatebe K, Chmura SJ, De Henau O, Gigoux M, Liu C, Mazo Ludwig San Diego
Pitroda SP, Gilbert JA, Fu YX, G, Deng L, Barker CA, Wolchok Science 2021 January 1
Nature Immunology
Weichselbaum RR. JD, Merghoub T.
2020 October 5 Online A tripartite mechanism
ahead of print catalyzes Mad2-Cdc20 assembly
Science Advances Journal of Experimental at unattached kinetochores.
Disturbed mitochondrial
2020 October 2 Medicine
dynamics in CD8+ TILs reinforce Lara-Gonzalez P; Kim T; Oegema
2020 December 29
Nanoscale metal-organic T cell exhaustion. K; Corbett K; Desai A
frameworks for x-ray activated Nuclear receptor LXRβ controls
Yu YR, Imrichova H, Wang H, Chao
in situ cancer vaccination. fitness and functionality of
T, Xiao Z, Gao M, Rincon-Restrepo
LUDWIG LINK | APRIL 2021
activated T cells. Science 2020 December 17
Ni K, Lan G, Guo N, Culbert A, Luo M, Franco F, Genolet R, Cheng Online ahead of print
T, Wu T, Weichselbaum RR, Lin W. WC, Jandus C, Coukos G, Jiang Michaels AJ, Campbell C, Bou-
YF, Locasale JW, Zippelius A, Liu Puerto R, Rudensky AY. HSP70 chaperones RNA-
PS, Tang L, Bock C, Vannini N, free TDP-43 into anisotropic
Ho PC. intranuclear liquid spherical
Ludwig Harvard Proceedings of the National shells.
Academy of Sciences USA
Nature Cancer Yu H, Lu S, Gasior K, Singh D,
2020 December 14 Epub
2020 December 14 Ludwig MIT Vazquez-Sanchez S, Tapia O,
FXR mediates T cell-intrinsic Toprani D, Beccari MS, Yates
Targeting immunosuppressive Molecular Cell responses to reduced feeding JR 3rd, Da Cruz S, Newby JM,
macrophages overcomes PARP 2020 December 22 Online ahead during infection. Lafarga M, Gladfelter AS, Villa E,
inhibitor resistance in BRCA1- of print
associated triple-negative Campbell C, Marchildon F, Cleveland DW.
breast cancer Increased demand for NAD+ Michaels AJ, Takemoto N, van der
relative to ATP drives aerobic Veeken J, Schizas M, Pritykin Y,
Mehta AK, Cheney EM, Guerriero Nature
glycolysis. Leslie CS, Intlekofer AM, Cohen P,
JL. 2020 December 23 Epub
Luengo A, Li Z, Gui DY, Sullivan Rudensky AY.
Chromothripsis drives the
LB, Zagorulya M, Do BT, Ferreira
Molecular Cell evolution of gene amplification
R, Naamati A, Ali A, Lewis
2020 October 30 Epub CA, Thomas CJ, Spranger S, Ludwig Oxford in cancer.
3D Culture Models with CRISPR Matheson NJ, Vander Heiden MG. Nature Communications Shoshani O, Brunner SF, Yaeger
Screens Reveal Hyperactive 2021 January 27 R, Ly P, Nechemia-Arbely Y, Kim
NRF2 as a Prerequisite for DH, Fang R, Castillon GA, Yu M, Li
Subtraction-free and bisulfite-
Spheroid Formation via JSZ, Sun Y, Ellisman MH, Ren B,
free specific sequencing of
Regulation of Proliferation and Campbell PJ, Cleveland DW.
5-methylcytosine and its
Ferroptosis. oxidized derivatives at base
Takahashi N, Cho P, Selfors LM, resolution.
Kuiken HJ, Kaul R, Fujiwara Liu Y, Hu Z, Cheng J, Siejka-
T, Harris IS, Zhang T, Gygi SP, Zielińska P, Chen J, Inoue M,
Brugge JS. Ahmed AA, Song CX.
25You can also read
