Epigenetics Dream Team II - Stand Up To Cancer

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Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team: The Epigenetics Dream Team II

Grant Term: October 2014–December 2022

Epigenetic therapy is an approach to cancer treatment that involves switching key genes on or off to help destroy cancer cells. The Van Andel Institute (VAI)–Stand Up To Cancer Epigenetics Dream Team II continues the original Epigenetics Dream Team’s work to restore normal function to damaged epigenetic mechanisms. To do this, the team employs clinical trials exploring immune sensitization, chemo sensitization and novel target strategies.

Supported by:

About This Team’s Research

Epigenetics describes biological processes that cells use to control whether genes are turned on or off without altering the DNA itself. Disrupting epigenetic mechanisms can drive the development of cancer.

Unlike genetic changes, epigenetic modifications are frequently reversible, thus providing opportunities for a new kind of therapy called epigenetic therapy. Using this tactic, targeted therapies cause specific epigenetic changes that return the expression of DNA to its precancerous condition.

Building on the successes of the original SU2C Epigenetics Dream Team, the VAI–SU2C Epigenetics Dream Team II continues to apply epigenetic therapies in combination with other treatments to multiple types of cancer, with clinical trials in three categories: immune sensitization, chemo sensitization and novel target strategies.

In its immune sensitization work, the team has combined epigenetic agents with immune checkpoint therapy in lung, blood and multiple solid cancer patients.

The team’s chemo sensitization strategy involves testing a new epigenetic agent on chemotherapy-resistant colorectal cancer.

The novel targeting strategies category comprises multiple projects including a trial using an epigenetic agent with a PARP inhibitor in acute myeloid leukemia patients and a study of combining a vitamin C supplement with epigenetic agents in blood cancer patients.


The top scientists and researchers on the VAI–SU2C Epigenetics Dream Team II come from a variety of backgrounds and disciplines, which leads them to great insights upon collaboration. Learn more about the VAI–SU2C Epigenetics Dream Team II.

Dream Team Members

Peter A. Jones, PhD, DSc
Van Andel Institute

Stephen Baylin, MD
Johns Hopkins University

Nilofer Azad, MD
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University
Principal Investigator

Maria Baer, MD
University of Maryland
Principal Investigator

Anthony El-Khoueiry, MD
University of Southern California
Principal Investigator

Kirsten Grønbæk, MD
University of Copenhagen/Rigshospitalet
Principal Investigator

Jean-Pierre Issa, MD
Coriell Institute for Medical Research
Principal Investigator

Kathy Miller, MD
University of Indiana
Principal Investigator

Kenneth Nephew, PhD
Indiana University School of Medicine
Principal Investigator

Casey O’Connell, MD
University of Southern California
Principal Investigator

Charles Rudin, MD, PhD
Memorial Sloan Kettering Cancer Center
Principal Investigator

Benjamin Youngblood, PhD
St. Jude Children’s Research Hospital
Principal Investigator

Penny Berger
Van Andel Institute
Project Manager

Ryan Burgos
Van Andel Institute
Project Manager

Revathi Penumatsa
Van Andel Institute
Project Manager

Andrea Poma
Van Andel Institute
Collaboration Project Manager

Beth Flory
Patient Advocate

“There’s a time for individual competition and a time for teamwork. And I think this is the time for teamwork in this particular area. We’ve competed against each other for years … We really need to get together now and make a big push.”

Peter A. Jones, PhD, DSc (hon)
Van Andel Institute


Stand Up To Cancer’s research projects are designed to foster collaborative, swift translational research. The hallmarks of these efforts include rigorous application and selection procedures, sufficient funding to allow scientists to focus on the objectives of the grant, and reviews by senior scientists every six months. These reviews help the investigators capitalize on the latest findings, address potential roadblocks, and collaboratively evolve as the science requires. Please click on the link to see summaries of research results so far for the VAI–SU2C Epigenetics Dream Team II.



Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer
Topper MJ, Velculescu V, Baylin SB, et al. (2017)
The emerging role of epigenetic therapeutics in immuno-oncology
Topper MJ, Vaz M, Marrone KA, Brahmer JR, Baylin SB (2020)
Nat Rev Clin Oncol 17(2):75–90
Epigenetic therapy inhibits metastases by disrupting premetastatic niches
Lu Z, Zou J, Li S, et al. (2020)
Nature 579(7798):284–290
Pharmacologic induction of innate immune signaling directly drives homologous recombination deficiency
McLaughlin LJ, Stojanovic L, Kogan AA, Rutherford JL, Choi EY, Yen RC, Xia L, Zou Y, Lapidus RG, Baylin SB, Topper MJ, Rassool FV. (2020)
Proc Natl Acad Sci U S A 117(30):17785–17795
Defining UHRF1 domains that support maintenance of human colon cancer DNA methylation and oncogenic properties
Kong X, Chen J, Xie W, Brown SM, Cai Y, Wu K, Fan D, Nie Y, Yegnasubramanian S, Tiedemann RL, Tao Y, Chiu Yen RW, Topper MJ, Zahnow CA, Easwaran H, Rothbart SB, Xia L, Baylin SB. (2019)
Cancer Cell 35(4):633–648.e7
DNA methyltransferase inhibitors induce a BRCAness phenotype that sensitizes NSCLC to PARP inhibitor and ionizing radiation
Abbotts R, Topper MJ, Biondi C, et al. (2019)
Proc Natl Acad Sci U S A 116(45):22609–22618
Genomic and epigenomic predictors of response to guadecitabine in relapsed/refractory acute myelogenous leukemia
Clin Epigenet 11(1):106
Defining UHRF1 domains that support maintenance of human colon cancer DNA methylation and oncogenic properties
Kong X, Chen J, Xie W, Brown SM, Cai Y, Wu K, Fan D, Nie Y, Yegnasubramanian S, Tiedemann RL, Tao Y, Yen RWC, Topper MJ, Zahnow CA, Easwaran H, Rothbart SB#, Xia L#, Baylin SB#. 2019
Cancer Cell
Enhancing the cytotoxic effects of PARP inhibitors with DNA demethylating agents–a potential therapy for cancer
Muvarak NE, Chowdhury K, Xia L, Robert C, Choi EY, Cai Y, Bellani M, Z Y, Singh ZN, Duong VH, Rutherford T, Nagaria P, Bentzen SM, Seidman MM, Baer MR, Lapdius RG, Baylin SB, Rassool FV. In press
Can Cell
Vitamin C increases viral mimicry induced by 5-aza2’-deoxycytidine
Proc Natl Acad Sci USA
Liu M, Ohtani H, Zhou W, Ørskov AD, Charlet J, Zhang YW, Shen H, Baylin SB, Liang G, Grønbæk K, Jones PA
PARP inhibitor activity correlates with SLFN11 expression and demonstrates synergy with temozolomide in small cell lung cancer
Lok BH, Gardner EE, Schneeberger VE, Ni A, Desmeules P, Rekhtman N, de Stanchina E, Teicher BA, Riaz N, Powell SN, Poirier JT, Rudin CM. In press
Clin Cancer Res
Hypomethylation of TET2 target genes identifies a curable subset of acute myeloid leukemia
Yamazaki J, Taby R, Jelinek J, Raynal NJ, Cesaroni M, Peirce SA, Kornblau SM, Bueso-Ramos CE, Ravandi F, Kantarjian HM, Issa JP. (2016)
J Natl Cancer Inst 108(2).
Safety and tolerability of guadecitabine (SGI-1110) in patients with myelodysplastic syndrome and acute myeloid leukemia: A multicenter, randomized dose-escalation phase 1 study
Issa JP, Roboz G, Rizzieri D, Jabbour E, Stock W, O’Connell C, Yee K, Tibes R, Griffiths EA, Walsh K, Daver N, Chung W, Naim S, Taverna P, Oganesian A, Hao Y, Lowder JN, Azab M, Kantarijian H. (2015)
Lancet Oncol 16(9):1099–1110
DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts
Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY, Han H, Liang G, Jones PA, Pugh TJ, O’Brien C, De Carvalho DD. (2015)
Cell 162(5):961–973
Inhibiting DNA methylation causes an interferon response in cancer via dsRNA including endogenous retroviruses
Chiappinelli KB, Strissel PL, Desrichard A, Li H, Henke C, Akman B, Hein A, Rote NS, Cope LM, Snyder A, Makarav V, Buhu S, Slamon DJ, Wolchok DJ, Pardoll DM, Beckmann WM, Zahnow CA, Mergoub T, Chan TA, Baylin SB, Strick R. (2015)
Cell 162(5):974–986
TET2 mutations affect non-CpG island DNA methylation at enhancers and transcription factor-binding sites in chronic myelomonocytic leukemia
Yamazaki J, Jelinek J, Lu Y, Cesaroni M, Madzo J, Neumann F, He R, Taby R, Vasanthakumar A, Macrae T, Ostler KR, Kantaijian HM, Liang S, Estecio MR, Godley LA, Issa JP. (2015)
Cancer Res 75(14):2833–2843
See MoreLess Publications


Cancer clinical trials allow researchers to study innovative and potentially life-saving new treatments. The goal is to find treatments that are better than what’s currently available; in fact, the therapies offered to today’s cancer patients were almost all studied and made possible by people participating in clinical trials. But many cancer clinical trials aren’t completed because not enough people take part.

At StandUpToCancer.org/ClinicalTrials, you’ll find clinical trial information, answers to common questions, and a free clinical trial finder tool.



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