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The 2023 Tisch Cancer Institute Specialty Report is now available.
The report highlights some of TCI’s significant findings and developments during the past year.
“At The Tisch Cancer Institute, we are investigating the complexities of cancer biology and behavior with the goal of improving the lives of those affected by cancer and minimizing its power. We do this collaboratively with our colleagues across the Mount Sinai Health System and the national and international arenas of cancer.” (Welcome From the Director)
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Ronald Hoffman, MD, is Principal Investigator on a P01 grant from the National Cancer Institute, which has received continuous funding since 2006, with the most recent renewal occurring in 2023. The grant supports The Myeloproliferative Neoplasm Research Consortium (MPN-RC), an inter-active group of laboratory and clinical scientists from 13 institutions throughout North America who work together to generate the scientific foundation for novel therapeutic strategies which can be evaluated in rigorous, well-constructed independent investigator-initiated clinical trials. The focus of the current grant renewal is on the myeloproliferative neoplasm myelofibrosis (MF). To improve MF patient survival, Dr. Hoffman and team hypothesize that the use of drugs, which act by directly targeting malignant hematopoietic stem cells and/or by correcting their tumor promoting microenvironments, will deplete the numbers of cancer stem cells.
The research components and leaders are:
- Project 1: Molecular Pathogenesis and Therapy of Myelofibrosis. Ross L. Levine, MD, Memorial Sloan Kettering Cancer Center
- Project 2: Defining the Role of Megakaryocyte Abnormalities in the Progression of Primary Myelofibrosis. John Crispino, PhD, MBA, St. Jude Children’s Research Hospital; Anna Rita Migliaccio, PhD, Mount Sinai; Altius Institute for Biomedical Sciences
- Project 3: Development of Strategies to Deplete Myelofibrosis Stem Cells. Ronald Hoffman, MD, Mount Sinai
- Project 4: MPN-RC Clinical Consortium. John Mascarenhas, MD, and Marina Kremyanskaya MD, PhD, Mount Sinai; Ruben Mesa, MD, Wake Forest University School of Medicine
- Core A: Administrative. Ronald Hoffman, MD, and Tiffany Harvin, Mount Sinai
- Core B: Tissue Bank. Bridget Marcellino MD, PhD, Mount Sinai
- Core C: Biostatistics and Data Management. Amylou C. Dueck, PhD, Mayo Clinic Cancer Center
- Core D: Biomarkers and Bioinformatics. Raajit K. Rampal, MD, PhD, Memorial Sloan Kettering Cancer Center
Read More
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Myeloid Malignancy Workshop | |
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Jennifer Marti, MD, has rejoined the staff at Mount Sinai as a breast surgical oncologist and Assistant Professor of Surgery. After medical school and general surgery training at New York University, she completed advanced breast and endocrine surgical fellowships at Memorial Sloan Kettering Cancer Center and Yale School of Medicine. She practiced at Mount Sinai from 2011-2016, and then New York-Presbyterian (NYP)/Weill Cornell Medicine on the Upper East Side from 2016-2022; she also served as Site Director of Breast Surgery at NYP/Lower Manhattan Hospital.
Dr. Marti specializes in the treatment of benign and malignant disorders of the breast, and has expertise in numerous procedures including hidden-scar lumpectomy and nipple-sparing mastectomy. Her research interests focus on the study and development of new approaches to de-escalate care for patients with breast cancer and to minimize overtreatment of low-risk benign lesions and cancers. She has numerous peer-reviewed publications in this field and presents regularly at national meetings.
Dr. Marti sees patients at Mount Sinai-Union Square.
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Lakshmi Rajdev, MD, MS, joined Mount Sinai as Associate Professor of Medicine (Hematology and Medical Oncology) and Medical Director of Oncology at Mount Sinai Morningside. Dr. Rajdev’s specialty is Gastrointestinal (GI) Oncology with particular expertise in gastroesophageal and anal carcinoma; she will develop a robust clinical research program in these areas as well as HIV-associated cancers. Dr. Rajdev sees patients at both Mount Sinai Morningside and Mount Sinai West.
A nationally recognized investigator, Dr. Rajdev has chaired and co-chaired investigator-initiated and cooperative group studies. She serves on numerous scientific committees, including the Esophago-Gastric and Rectal Anal Task Force of the National Cancer Institute (NCI) GI Cancer Steering Committee and the NCI Adult Central Institutional Review Board Late Phase Emphasis Committee. She has held leadership roles in the Eastern Cooperative Oncology Group GI Committee and the AIDS Malignancy Consortium. Prior to joining Mount Sinai, Dr. Rajdev spent most of her career at Montefiore Medical Center/Albert Einstein Cancer Center. More recently, she served as Chief of Hematology and Oncology at Lenox Hill Hospital and Director of GI Malignancies for the Western Region of the Northwell Health System.
Dr. Rajdev earned her MBBS from Grant Medical College in Bombay. She completed Internal Medicine residencies at Grant Medical College and Beth Israel Medical Center, and fellowship in Hematology/Oncology at New York University. Dr. Rajdev also has a Masters in Clinical Research from Albert Einstein College of Medicine.
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Jian Jin, PhD, was elected as a National Academy of Inventors (NAI) Fellow and will be inducted at the NAI annual meeting on June 27, 2023. The NAI was founded in 2010 to recognize and encourage inventors with patents issued from the U.S. Patent and Trademark Office, enhance the visibility of academic innovation, and translate the inventions of its members to benefit society. Dr. Jin is the Mount Sinai Endowed Professor in Therapeutics Discovery, Director of the Mount Sinai Center for Therapeutics Discovery, and Co-leader of the Cancer Clinical Investigation Program at TCI. He has more than 70 issued U.S. patents and published international patent applications.
About the NAI Fellows Program
2022 Fellows
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Joshua Brody, MD, and Thomas Marron, MD, PhD, and their work on cancer vaccines were featured on FOX 5.
"Most of these cancer vaccines we are talking about are not to prevent cancer but to treat someone who already has cancer," Dr. Brody said. "So instead of a preventative vaccine we call it a therapeutic vaccine for someone who already has the problem."
"We're taking patients who have a tumor and we are creating a vaccine inside the tumor. We are teaching the immune system inside the tumor what the tumor looks like because the goal is not just to kill the tumor that we're treating with the different components of the vaccine but also to teach the immune system to kill the cancer everywhere in the body," said Dr. Marron.
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Ramon Parsons, MD, PhD, was selected to receive the 2023 Jacobi Medallion. Recipients have made exceptional contributions to the Icahn School of Medicine at Mount Sinai, the Mount Sinai Health System, the Mount Sinai Alumni Association, or the fields of general medicine or biomedicine. The award ceremony will be held on March 15.
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Doris Germain, PhD, was awarded R21 grant funding from the National Cancer Institute to study the protective role of breastfeeding against breast cancer. While breastfeeding is protective against breast cancer, the mechanism remains unknown. This R21 builds on a mouse model developed in the Germain Lab, which showed that long lactation completely inhibits the formation of mammary tumors. Dr. Germain and team will test the hypothesis that a hormone secreted by the ovaries during lactation is the mediator of the protective effect.
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Saghi Ghaffari MD, PhD, received renewal of her R01 grant—Mitochondria in the Regulation of Terminal Erythropoiesis—from the National Heart, Lung, and Blood Institute. In this renewal, Dr. Ghaffari will investigate the adenosine triphosphate (ATP)-independent functions of mitochondria in the regulation of red blood cell (RBC) production, identify the related signaling molecules involved, and evaluate the effect of their potential alterations in disease with the ultimate goal of improving therapies of erythroid disorders and the ex vivo production of RBCs.
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Ajai Chari, MD, and colleagues
Talquetamab, a T-cell–redirecting GPRC5D bispecific antibody for multiple myeloma
New England Journal of Medicine. 2022 December 10. PMID: 36507686
Talquetamab, an off-the-shelf bi-specific antibody, elicited overall response rates of more than 70 percent when administered in heavily pretreated patients with relapsed or refractory multiple myeloma, according to updated data from the phase 1/2 MonumenTAL-1 trial (NCT03399799, NCT04634552). Talquetamab targets GPRC5D, a receptor expressed on the surface of cancer cells. The excellent responses, maintained in multiple myeloma subgroups including high-risk disease, suggest that talquetamab may offer a viable option for patients whose myeloma no longer responds to other therapies.
Press Release
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Emily Bernstein, PhD, and colleagues
MacroH2A impedes metastatic growth by enforcing a discrete dormancy program in disseminated cancer cells
Science Advances. 2022 Dec 2. PMID: 36459552
This study reveals that macroH2A histone variants can suppress head and neck squamous cell carcinoma metastasis by tapping into a set of genes found in senescent and dormant cells, suggesting that activating a subset of components of distinct growth arrest programs may be sufficient to induce and maintain dormancy. Detection of macroH2A histone variants in primary lesions or in disseminated cancer cells (DCCs) might be useful biomarkers of patients with better prognosis and/or dormant DCCs.
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Yan Xiong, PhD; Jian Jin, PhD; and colleagues
Bridged Proteolysis Targeting Chimera (PROTAC) enables degradation of undruggable targets
Journal of the American Chemical Society. 2022 Dec 14. PMID: 36448571
Dr. Jin and team developed a new technology, termed as bridged PROTAC, for targeting undruggable proteins which lack small-molecule binders. Bridged PROTAC utilizes a small-molecule binder of the target protein’s binding partner to recruit the protein complex into close proximity with an E3 ubiquitin ligase to target undruggable proteins. Applying this technology, the team discovered MS28, the first degrader of cyclin D1, which is undruggable and a top cancer target. MS28, which is a CDK4/6-binding PROTAC, preferentially degraded cyclin D1 over CDK4/6. Bridged PROTAC as a novel PROTAC strategy provides a generalizable platform for targeting undruggable proteins and expands the targetable human proteome.
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Susana Ramos, PhD; Nadia Tsankova, MD, PhD; and colleagues
An atlas of late prenatal human neurodevelopment resolved by single-nucleus transcriptomics
Nature Communications. 2022 Dec 12. PMID: 36509746
Using a comprehensive single-nucleus RNA sequencing dataset of second and third-trimester human neocortical development, Dr. Tsankova and team uncover a novel cell type transiently present during late prenatal human brain development, and demonstrate that its signature is broadly recapitulated across pediatric and adult glioblastoma tumors. They speculate that further studies into glial intermediate progenitor cell lineage-specific transcription factors and their regulatory networks may facilitate the discovery of novel therapeutic targets in glioblastoma.
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TCI Seminar Series
January 17, Noon, Davis Auditorium
Riccardo Dalla-Favera, MD
The Herbert Irving Comprehensive Cancer Center, Columbia University
Genomics of B cell Lymphoma: The Emerging Role of Mutations in Non-Coding Regulatory Domains
January 24, Noon, Davis Auditorium
Marina Konopleva, MD, PhD
Blood Cancer Institute, Montefiore/Einstein
Targeting Apoptotic Machinery in Leukemia: BCL-2 and Beyond
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Applications are being accepted for the TCI Summer Scholars Program. The program provides research stipends for medical students at the Icahn School of Medicine at Mount Sinai to conduct original cancer research in clinical, translational, basic, epidemiological, or health services disciplines.
Application deadline: March 27
Application Information
Testimonials from last summer’s students Ayman Mohammad and Nina Rodriguez:
- The fellowship experience cemented my dream of serving at the cutting edge of therapeutic investigation in oncology.
- The best part was getting to see patients every week.
- The program helped me develop mentoring relationships with the physicians I worked with.
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The TCI Research Retreat, held on December 14, culminated in awards for the best posters. The Grand Prize ($1,500) winner was Yue Zhong from Dr. Jian Jin’s lab (Cancer Clinical Investigation). Honorable Mention awards ($500 each) went to Matthew Brown and Ashley Reid, both from Dr. Nina Bhardwaj’s lab (Cancer Immunology). Posters were judged by a faculty team representing basic science, translational research, clinical research, and population science. The award dollars are designated for attendance at cancer conferences.
Yue Zhong, PhD student: Bridged Proteolysis Targeting Chimera (PROTAC) Enables Degradation of Undruggable Targets
Ashely Reid, PhD student: Targeting Treatment-Dependent Repeat-Derived Antigens for Melanoma Vaccination
Matthew Brown, MSCR, PhD student: Interrogating Frameshift Neoantigen-Specific T Cell Dynamics in Mismatch Repair Deficient Tumor Development
Matthew earned his Master of Science in Clinical Research at the Graduate School of Biomedical Sciences at the Icahn School of Medicine at Mount Sinai.
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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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