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James Ferrara, MD, is Principal Investigator on a Program Project (P01) grant from the National Cancer Institute—Cellular and Molecular Studies of Bone Marrow Transplant—which has received continuous funding since 1997, with the most recent renewal extending through 2027. The goal of the P01 is to reduce graft-versus-host disease (GVHD), a major cause of morbidity and mortality after allogeneic stem cell transplant, by elucidating its basic biology, developing laboratory strategies to predict its long term outcomes, and translating findings into novel therapeutic strategies via Phase II clinical trials.
Using pioneering proteomic techniques, the Ferrara Bone Marrow Transplant Laboratory has identified and validated biomarkers for skin, gut, and steroid-resistant GVHD, and developed the first algorithm that predicts GVHD prior to symptom onset. The capacity of biomarkers to guide therapy led to the establishment in 2014 of MAGIC (Mount Sinai Acute GVHD International Consortium), comprising 25 bone marrow transplant centers across the U.S., Europe, and Asia that conduct clinical trials to prevent and treat acute GVHD.
Acute GVHD in the gastrointestinal (GI) tract accounts for the majority of non-relapse mortality. The mechanisms of damage to the GI crypt during GVHD and enhancing its regeneration are the focus of the current funding cycle across the three projects of the P01. Specifically, Project 1, led by Pavan Reddy, MD, at the University of Michigan, and Project 2, led by Dr. Ferrara, focus on the role of mitochondrial damage in intestinal stem cells and the role of the enzyme RIP1 that causes their death. Project 3, led by John Levine, MD, focuses on two risk-adapted clinical trials that determine treatment based on GI damage as measured by serum biomarkers.
Recent publications:
Grand Rounds with Dr. Ferrara: Mapping the future of Hemopoietic Cell Transplants: MAGIC Biomarkers
Grand Rounds with Dr. Levine: Transforming GVHD Treatment: The Mount Sinai Acute GVHD International Consortium (MAGIC)
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Ana Acuna-Villaorduna, MD, MSc, has joined Mount Sinai as Assistant Professor of Medicine (Hematology and Medical Oncology) and Clinical Assistant Director of the Cancer Immunotherapy Program at The Tisch Cancer Institute. Originally from Peru, Dr. Acuna earned her MD at Universidad Peruana Cayetano Heredia. She completed residency at Jacobi Medical Center/Albert Einstein College of Medicine (Einstein) and Hematology/Oncology Fellowship at Montefiore Medical Center/Einstein. She also has a Master of Science in Clinical Research from Einstein. Dr. Acuna most recently served as Medical Director for the Phase I Program and attending physician in Gastrointestinal Oncology at Montefiore-Einstein. She has a particular interest in developmental therapeutics and translational research in solid malignancies. As a recipient of the 2020 ASCO Young Investigator Award and the 2021 Robert A. Winn Award from the Bristol Myers Squibb Foundation, Dr. Acuna has received national recognition for her work in addressing racial disparities and improving access to innovative cancer care. In her role as Clinical Assistant Director for the Cancer Immunotherapy Program, led by Nina Bhardwaj, MD, PhD, she will also partner with the Early Phase Trial Unit led by Thomas Marron, MD, PhD, with the ultimate goal of expanding access to novel therapeutic treatment options to patients across the entire Mount Sinai Health System, especially in minority populations. Dr. Acuna will see patients at the Ruttenberg Treatment Center and Mount Sinai West.
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Cancer Network Physicians | |
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Agnes Radzio, MD, MS, is Associate Professor of Surgery and Director of Breast Surgery at Mount Sinai Doctors-Staten Island. In practice for more than 15 years, she specializes in breast surgical oncology and has expertise in BRCA and other genetic mutations. Dr. Radzio earned her MD from Northwestern University Feinberg School of Medicine. She completed surgical residency at Thomas Jefferson University and fellowship in Breast Surgery at the University of California San Francisco. Dr. Radzio also holds a MS in Biotechnology Specialization from the Kellogg Center for Biotechnology at Northwestern University. She speaks English, Polish, and Russian.
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Anjali Budhathoki, MD, is Assistant Professor of Medicine (Hematology and Medical Oncology). She focuses on general hematology as well as breast, genitourinary, and gastrointestinal oncology, and sees patients at Mount Sinai Queens and Mount Sinai Doctors Jackson Heights. Dr. Budhathoki received her MD from B.P. Koirala Institute of Health Sciences in Nepal. She completed residency in Internal Medicine at St. Vincent’s Hospital in NYC and fellowship in Hematology/Oncology at Albert Einstein College of Medicine/Montefiore Medical Center. Prior to joining Mount Sinai, Dr. Budhathoki practiced in the rural, underserved community of Aberdeen, South Dakota. She speaks English and Nepali.
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Nina Bhardwaj, MD, PhD, has been appointed as Associate Director of the Scientific Advisory Council of the Cancer Research Institute (CRI). In this role, Dr. Bhardwaj will advise CRI on key matters related to overall research strategy. CRI fuels discovery and development of immunotherapies for all cancers.
Read More
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Amir Horowitz, PhD, and John Sfakianos, MD, are Co-Principal Investigators on their first R01 from the National Cancer Institute. Their project, HLA-E and NKG2A Define a Novel Immune Checkpoint Axis in Non-Muscle-Invasive Bladder Cancer, will investigate whether combination NKG2A/programmed cell death ligand-1 (PD-L1) blockade promotes antitumor immunity in bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) and how response to NKG2A/PD-L1 blockade correlates with ex vivo expression of NKG2A/HLA-E and PD-1/PD-L1 on NK and CD8 T cells and tumors, respectively. They will also examine how response correlates to expression of any additional inhibitory checkpoint pathways; this will provide insights into the likelihood and causal drivers of secondary resistance. Previously, Dr. Horowitz and Dr. Sfakianos demonstrated a unique working model of tumor recurrence after BCG exposure, identifying HLA-E/NKG2A as a novel immune checkpoint axis that may enhance sensitivity to NKG2A blockade. | |
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Jose Javier Bravo-Cordero, PhD, received an Emerging Leader Award from The Mark Foundation for his project, Impact of Dormant Cancer Cells on the Brain Microenvironment. He will use high-resolution imaging technology to understand how dormant cancer cells instruct neuronal tissue at the single cell level. Emerging Leader Awards recognize outstanding early-career investigators who are addressing unmet needs in cancer research.
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Doris Germain, PhD, received funding from The Chemotherapy Foundation in support of her study of the mechanisms underlying the protective role of breastfeeding against breast cancer. Dr. Germain and team will test the hypothesis that a hormone secreted by the ovaries during lactation is the mediator of the protective effect. Dr. Germain also received renewed funding from the Samuel Waxman Cancer Research Foundation for her project on the link between aging and breast cancer.
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Four research teams have received 2022 TCI Developmental Fund Awards from The Tisch Cancer Institute and the ConduITS Institute for Translational Sciences. These awards support translational and/or epidemiological projects that are intra-and inter-collaborations between TCI members.
Deborah Doroshow, MD, PhD (Cancer Clinical Investigation); Melissa Mazor, PhD, MS, RN (Cancer Prevention and Control)
Development and Evaluation of a Lay Navigator-Led Intervention for Enhancing Diversity in Early Phase Clinical Trial Enrollment
Bridget Marcellino, MD, PhD (Cancer Clinical Investigation); Elvin Wagenblast, PhD (Cancer Mechanisms)
Therapeutic Vulnerabilities in High-Risk CRLF2-rearranged Lymphoblastic Leukemia
Deirdre Cohen, MD (Cancer Clinical Investigation); Benjamin Hopkins, PhD (Cancer Mechanisms); Daniela Sia, PhD (Cancer Mechanisms); Anna Tocheva, PhD (Cancer Immunology)
Validating a Patient-Derived Pre-Clinical Model of Intrahepatic Cholangiocarcinoma That Accurately Recapitulates Patient Responses to Identify Novel Immunotherapy-Based Combinations
Daniel Puleston, PhD (Cancer Immunology); Myron Schwartz, MD (Cancer Clinical Investigation)
Novel Approaches to Probe Human Hepatocellular Carcinoma Biology and Therapy Through Normothermic Machine Perfusion of the Liver
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Myvizhi Esai Selvan, PhD; Kenan Onel, MD, PhD; Sacha Gnjatic, PhD; Robert Klein, PhD; Zeynep Gümüş, PhD
Germline rare deleterious variant load alters cancer risk, age of onset and tumor characteristics
npj Precision Oncology. 2023 Jan 27.
PMID: 36707626
This paper reports on the largest-to-date whole-exome sequencing study in a case-control setting and identifies germline rare, deleterious variants (RDVs) in specific genes and gene-sets associated with multi-cancer risk. The study also reveals that the number of RDVs an individual has, or their RDV load, increases cancer risk, lowers age of onset, and alters tumor immune microenvironment and tumor mutational burden. Findings can be used to identify high-risk individuals who may benefit from increased surveillance, earlier screening, and treatments that exploit their tumor characteristics. Future studies will expand understanding of the nature of interactions between germline RDV load, tumor characteristics, and survival.
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Nina Bickell, MD, MPH, and colleagues
Centralization of initial care and improved survival of poor patients with breast cancer
Journal of Clinical Oncology. 2023 Jan 5. PMID: 36603178
Dr. Bickell and colleagues report on a study of the effectiveness of a policy intervention undertaken by New York State (NYS) in 2009 to improve outcomes for patients undergoing breast cancer surgery. Prior observational work found higher death rates among women treated at facilities performing fewer than 30 breast cancer surgeries annually. The policy precluded payment for breast cancer surgery for NYS Medicaid beneficiaries treated at these low volume facilities. Among the 37,822 women with stage I-III breast cancer treated pre- and post-policy, women with Medicaid had better survival rates from breast cancer post-policy suggesting this cost-neutral approach may reduce disparities in breast cancer outcomes
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M Margaret Kemeny, MD, and colleagues
Phase III prospectively randomized trial of perioperative 5-FU after curative resection for colon Cancer: An intergroup trial of the ECOG-ACRIN Cancer Research Group (E1292)
Annals of Surgical Oncology. 2023 Feb. PMID: 36305992
Based on studies suggesting that adjuvant chemotherapy should be initiated at the earliest possible time following curative colon resection, the Eastern Cooperative Oncology Group (ECOG) and Intergroup evaluated the effect of perioperative fluorouracil (5-FU) on overall survival (OS) for colon cancer. The trial found no statistically significant difference in OS or disease-free survival among patients with Dukes’ B2, B3, and C colon cancer. Fifteen-year follow up showed a six-year difference in survival for the Dukes B2 patients who only received one week of peri-operative 5FU and a one-year difference for the Stage 3 patients. Also, findings showed that 5FU given within 24 hours of completion of colon surgery did not cause increased operative complications.
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Jian Jin, PhD, and colleagues
Targeted degradation of PRC1 components, BMI1 and RING1B, via a novel protein complex degrader strategy
Advanced Science. 2023 Feb 3.
PMID: 36737841
Dr. Jian Jin and team discovered MS147, the first small-molecule degrader of polycomb repressive complex 1 (PRC1) components, BMI1 and RING1B, using the bridged PROTAC technology developed by the Jin lab, which is a novel protein complex degradation strategy to target undruggable proteins. MS147, which is an EED-binding and VHL E3 ligase-recruiting PROTAC, preferentially degraded PRC1 components BMI1 and RING1B over PRC2 components such as EED, EZH2 and SUZ12, and effectively suppressed the proliferation in cancer cell lines that are not dependent on EZH2/PRC2.
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Spotlight on Clinical Trials | |
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Amy Tiersten, MD, is leading two investigator-initiated clinical trials for metastatic breast cancer that are open to patient accrual.
A Multicenter, Phase IB/II Study of Abemaciclib in Combination with Bicalutamide for Androgen Receptor-positive, HER2-negative Metastatic Breast Cancer
Mount Sinai Protocol Number 21-0699
NCT05095207
With the Phase I dose-finding portion completed, the trial is now in Phase II dose expansion. Biclutamide has known activity in androgen receptor-positive metastatic breast cancer. Preclinical data suggest that the addition of abemaciclib may enhance efficacy. The regimen has been well tolerated thus far.
A Multi-Center Randomized Phase II Comparison of Single-Agent Carboplatin Versus the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer
Mount Sinai Protocol Number 15-1075
NCT02531932
Carboplatin is a known active agent for triple-negative breast cancer. A prior phase II trial of carboplatin/everolimus showed good efficacy and tolerability.
These clinical trials and others can be found at
https://oncore-search.mssm.edu/index.
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Monday, February 13, 2 pm via Zoom
Nicolas Vabret, PhD
Harnessing Viral Mimicry Drugs to Improve Cancer Vaccination
Zoom Info
Tuesday, February 14, 12-1 pm, Davis Auditorium, The Leon and Norma Hess Center for Science and Medicine
Chris Jones, PhD, The Institute of Cancer Research, London
Forward and Reverse Translational Studies in Pediatric-Type Diffuse High Grade Glioma
Friday, February 17, 4-5:30 pm, Goldwurm Auditorium, Icahn Building
Heidi Rehm, PhD, Center for Genomic Medicine, Massachusetts General Hospital
Advancing Genomic Medicine Through Collaboration on a Global Scale
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Community Outreach and Engagement | |
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The latest TCI Community Outreach and Engagement Newsletter focuses on cancer screening and community outreach activities in honor of National Cancer Prevention Month.
Community Outreach and Engagement Leadership:
Cardinale B. Smith, MD, PhD, Associate Director
Lina Jandorf, MA, Director, Cancer Community Outreach
Melissa Mazor, PhD, MS, RN, Nurse Scientist
Alison Snow, PhD, LCSW-R, OSW-C, Director, Cancer Community Engagement
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Congratulations to Julia Blanter, MD, Fellow (PGY4), Hematology and Medical Oncology, named as Fellow of the Month. Julia was recognized as a "dream co-fellow, a true leader and inspiration to us all."
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Ahmed Elsaadi, mentored by Jerry Edward Chipuk, PhD, defended his Master of Science in Biomedical Science, Icahn School of Medicine at Mount Sinai, on January 11. His work—The ATF5-Dependent Mitochondrial Unfolded Protein Response Impacts Mitochondrial Biology and Proliferation in BRAFV600E Primary Melanoma Models—evaluated the impact of organelle stress signaling on mitochondrial bioenergetics, metabolism, and senescence in multiple models of primary melanoma.
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New Benign Hematology Conference to Begin February 14
Organized by Johnson Liu, MD, and Ronald Hoffman, MD, a new benign hematology conference series will take place, primarily via Zoom, every second and fourth Tuesday from 4 to 5 pm.
Intended Audience: Hematology/Oncology faculty and fellows; disease team members; and scientists, residents, and students interested in hematology
More Information
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Do you have news for the next issue of TCI Connections?
Please send to Janet Aronson (646-745-6376).
Remember to share breaking news and high impact news that might be appropriate for media coverage with Marlene Naanes (929-237-5802) in the Press Office. This may include pending FDA drug/device approvals, studies/trial results being published in high-impact journals, and patient stories. The more lead time you can give Marlene, the better—ideally, four weeks or when a paper is accepted by the journal. Embargoes will always be honored and news will only be released with your approval.
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Ramon Parsons, MD, PhD, Director
Janet Aronson , Editor
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