November/December 2022

Dear TCI Community,

It is always good at the holiday season to reaffirm our mission of advancing basic, clinical, and population health cancer research with the goals of preventing cancer and improving the lives of those who face the challenges of cancer. All of us at TCI support this mission every day with passion, commitment, ingenuity, and collaboration.

Through our relentless studies of the biology and behavior of cancer, our drive to decipher the mechanisms that enable cancer to resist treatment and evade detection, and our compassion for patients and their loved ones, we are making a difference.

The TCI Research Retreat on December 15 will showcase our research and directions for future investigation, as well as the exciting strengths of our newest faculty members. The retreat is a wonderful opportunity to reignite our energies; I hope you will join us.

I am exceedingly proud of every member of the TCI team and our collective excellence. My appreciation to all for the bright accomplishments of 2022. And best wishes for a safe, healthy, and joyous holiday season.

Ramon Parsons, MD, PhD

TCI Research Retreat 2022

New Faculty, New Technology, and New Advances in

Diagnostics and Treatment

Wednesday, December 14

8:30 am – 5 pm

New York Academy of Medicine

Registration and Poster Abstract Submission

Agenda

In this special Science supplement—Frontiers of Medical Research: Cancer—TCI researchers describe advancements that are leading to a better understanding of the molecular and cellular underpinnings of cancer and ways to leverage these discoveries to develop new approaches that target specific features of tumor cells.

Caitlin Carr, MD, joined Mount Sinai as Assistant Professor in the Department of Obstetrics, Gynecology, and Reproductive Science (Division of Gynecologic Oncology). Dr. Carr earned her MD from the University of Tennessee College of Medicine. She completed residency in Obstetrics and Gynecology at the Cleveland Clinic Foundation, including a rotation in gynecologic oncology at the University of Texas MD Anderson Cancer Center, and fellowship training in gynecologic oncology at The Mount Sinai Hospital. Dr. Carr has a particular interest in advanced abdominal-pelvic and minimally invasive surgical procedures, management of patients with hereditary cancer syndromes, and clinical trials that advance novel chemotherapeutics. She has published in high-impact, peer-reviewed journals on topics that include clinicopathologic characteristics and outcomes of endometrial cancer patients with mismatch repair deficiency, long-term outcomes for single-port risk-reducing salpingo-oophorectomy for women at risk for gynecologic cancer, and racial disparities in patients with COVID-19 infection and gynecologic malignancy. Dr. Carr sees patients at The Blavatnik Family Chelsea Medical Center and Mount Sinai Doctors-Astoria.

Johnson M. Liu, MD, joined Mount Sinai as Professor of Medicine (Hematology and Medical Oncology) and Section Head for Hematology within the Division of Hematology and Medical Oncology. Dr. Liu was most recently at Maine Medical Center, where he held the Conley Family Endowed Chair in Hematology and served as Division Director of Hematology. His career has taken him to the National Heart, Lung, and Blood Institute; Albert Einstein College of Medicine; and the Zucker School of Medicine at Hofstra/Northwell, where he held the Les Nelkin Endowed Chair in Pediatric Oncology. He also was Associate Professor of Medicine and Director of Research with the Stem Cell Transplantation Program at Mount Sinai from 2002 to 2005. Dr. Liu’s research interests include molecular hematopoiesis and development, gene and cell therapy, bone marrow failure syndromes, genetic blood disorders, and transition of patients from pediatric to adult medicine. Dr. Liu sees patients at Mount Sinai-Union Square and the Ruttenberg Treatment Center.

Tingting Jiang, PhD, joined Mount Sinai as Assistant Professor with the Genomics Institute and the Department of Oncological Sciences. Her research focus is on expanding the application of CRISPR-based genome editing in studying extrachromosomal DNA mutations and modulating liver cancer drug resistance. Dr. Jiang earned her PhD from the National University of Singapore, where she studied the spatiotemporal regulation of signaling networks in tumorigenesis in the laboratory of Boon Chuan Low, PhD. During her postdoctoral studies with Wen Xue, PhD, at the University of Massachusetts Medical School she developed CRISPR technology to study determinants of liver cancer growth. 

Yizhou Dong, PhD, joined Mount Sinai as Professor of Oncological Sciences. Dr. Dong earned his PhD in Pharmaceutical Sciences from the University of North Carolina at Chapel Hill and did a postdoctoral fellowship with Robert Langer, ScD, and Daniel G. Anderson, PhD, at MIT. He was at Ohio State University since 2014, most recently as Associate Professor in the College of Pharmacy. Dr. Dong’s research focuses on the design and development of biotechnology platforms for the treatment of genetic disorders, infectious diseases, and cancers. He is Principal Investigator on multiple grants, including R35 and R01 grants from the National Institutes of Health. Dr. Dong is an elected fellow of the American Institute for Medical and Biological Engineering. 

Steven J. Burakoff, MD, was honored with the Mount Sinai Inventor of the Year Award at the eighth annual Mount Sinai Innovation Awards ceremony, held on October 24. Dr. Burakoff, Dean for Cancer Innovation at The Tisch Cancer Institute, was recognized for developing small molecule therapeutic inhibitors targeting HPK1 to regulate the immune response against cancer.

John Levine, MD, was honored with the Louis Aledort Clinical Research Professorship in Hematology at the Department of Medicine Convocation on November 30. Dr. Levine, Professor of Medicine (Hematology and Medical Oncology) and Pediatrics, is Co-director of the Mount Sinai Acute GVHD International Consortium (MAGIC).

Nina Bhardwaj, MD, PhD, is the recipient of the 2022 ESMO Award for Immuno-Oncology from the European Society for Medical Oncology in recognition of her outstanding contributions to cancer immunology research. Dr. Bhardwaj will deliver her award lecture on December 7 during the ESMO Immuno-Oncology Congress 2022.

Sundar Jagannath, MD, received the Michaeli Lifetime Achievement Award for Outstanding Contributions to Multiple Myeloma from the SASS-ARENA Foundation for Medical Research.

The award was presented on October 21 at the annual Lymphoma, Leukemia & Myeloma Congress. Hearn Jay Cho, MD, PhD, had the honor of introducing Dr. Jagannath.

Maria Soledad Sosa, PhD, received the 2022 Sue Eccles Early Career Investigator Award from the Metastasis Research Society. The award recognizes outstanding metastasis research performed by members of the MRS who are in their first faculty position after postdoctoral training and who have established their own independent research; it was presented at the MRS 19th Biennial Congress held in November in Buenos Aires.

Avi Ma’ayan, PhD, and his lab received the 2022 CBTN Pioneering Spirit Award at the annual meeting of the Children’s Brain Tumor Network for the work they presented—“Computational Screen to Identify Potential Targets for the CBTN Cohort"—at the 2022 CBTN Scientific Summit, held on October 17 in Washington, D.C.

Summit Agenda

Cesar Rodriguez, MD, was named a 2022 Multiple Myeloma Health Equity Hero by CURE Media Group in recognition of his efforts to promote health equity and address disparities in the multiple myeloma community. An award ceremony will be held on December 11, in conjunction with the annual meeting of the American Hematology Society.

Joshua Brody, MD, was awarded grant funding from the Follicular Lymphoma Foundation for “Preventing Antigen Escape After T Cell Therapies by Enhancing Fas-Mediated Bystander Killing.” The goal is to maximize the effectiveness of CAR T-cell therapy and thereby improve outcomes for patients.

Royce Zhou; Jia Xu, PhD; Ramon Parsons, MD, PhD; and colleagues

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma

Nature Communications. 2022 Oct 17. PMID: 36253360

In this study, using freshly resected primary colorectal carcinoma (CRC) tumors and patient-matched adjacent normal colon, Dr. Parsons and team find divergent epigenetic landscapes between CRC tumors and cell lines. They demonstrate that one CRC super-enhancer that regulates PDZK1IP1 in response to inflammation enhances the reductive capacity of CRC cancer cells via the pentose phosphate pathway and that this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Their findings broaden the understanding of super-enhancers and highlight the importance of epigenomic profiling of primary tumor specimens and patient-matched controls, and suggest that targeted therapy that reduces inflammation to lower the level of expression of PDZK1IP1 could benefit patients with colorectal cancer.

Video

Press Release

Oliver Van Oekelen, MD, MS, PhD; Samir Parekh, MD; and colleagues

Interventions and outcomes of multiple myeloma patients receiving salvage treatment after BCMA-directed CAR T therapy

Blood. 2022 Nov 3. PMID: 36327160

This study, the largest analysis of patients whose multiple myeloma relapses following BCMA-directed CAR T-cell therapies, demonstrates improved response rates for patients who receive additional T cell therapies as salvage therapy. The findings can serve as a benchmark for future prospective clinical studies aimed at improving the outcomes of multiple myeloma patients whose disease progresses after CAR T-cell therapy and who have a limited prognosis.

Press Release

John Mascarenhas, MD; Ronald Hoffman, MD; and colleagues

Biological drivers of clinical phenotype in myelofibrosis

Leukemia. 2022 Nov 24. PMID: 36434065

This cutting-edge review provides a pivotal summary of the most recent understanding of molecular and immune biology of myelofibrosis and associated treatment considerations, including treatment with JAK inhibitors and other novel agents tailored to genotype and phenotype for extended, deeper clinical benefit.

Judit Svensson-Arvelund, PhD; Joshua Brody, MD; Adolfo Garcia-Sastre, PhD; Miriam Merad, MD, PhD; Brian Brown, PhD; and colleagues

Expanding cross-presenting dendritic cells enhances oncolytic virotherapy and is critical for long-term anti-tumor immunity

Nature Communications. 2022 Nov 22. PMID: 36418317

Using lymphoma as a cancer model because of its unique sensitivity to various T cell-mediated immunotherapies, this study presents a detailed characterization of the immune response to Newcastle disease virus and the impact of increasing intratumoral dentritic cells (DCs) by administration of FLT3-ligand. The study demonstrates the benefit of expanding cross-presenting DCs in oncolytic virotherapy for achieving long-term anti-tumor immunity.

Emily Gallagher, MD, PhD; Derek LeRoith, MD, PhD; Elisa Port, MD; Nina Bickell, MD; and colleagues

Insulin resistance and racial disparities in breast cancer prognosis: a multi-center cohort study

Endocrine-Related Cancer. 2022 Nov 2. PMID: 36197762

This study of 1206 women with newly-diagnosed primary invasive breast cancer (BC) aimed to determine if homeostatic model assessment for insulin resistance (HOMA-IR) mediated part of the relationship between race and BC prognosis. The study included detailed metabolic studies and screening data and information on BC subtypes, advancing the understanding of the complex relationship between insulin resistance and racial disparities in BC prognosis. Overall, findings suggest that HOMA-IR contributes to the racial disparities in BC outcomes, particularly for women with HR-positive BCs.

David Mulholland, PhD; John Sfakianos, MD; Matthew Galsky, MD; Nina Bhardwaj, MD, PhD; Jun Zhu, PhD; and colleagues

Tumor-infiltrating myeloid cells confer de novo resistance to PD-L1 blockade through EMT-stromal and Tgfβ-dependent mechanisms

Molecular Cancer Therapeutics. 2022 Nov 3. PMID: 36129800

In this study, Dr. Mulholland and team completed a transcriptomic analysis of the tumor microenvironment of human and mouse muscle-invasive bladder tumors (MIBC). They assessed the heterogeneity in stromal and immune cell populations found in tumors that had received no previous immune checkpoint blockade ICB. This led to the identification of a conserved gene signature that may explain the presence of de novo resistance to PD-L1 blockade that occurs in a significant portion of patients with bladder cancer who have myeloid cell-high bladder tumors and poor clinical outcome.

Fionnuala Crowley, MD; Ashutosh Tewari, MD; Che-Kai Tsao, MD; Natasha Kyprianou, PhD; Dara Lundon, MD, PhD, MBA; and colleagues

Prostate cancer in transgender women: considerations for screening, diagnosis and management

British Journal of Cancer. 2022 Oct 19. PMID: 36261584

In this review, Dr. Lundon and colleagues discuss the evidence surrounding screening and treatment of prostate cancer in transgender women and consider the current gaps in knowledge in providing evidence-based guidance at the molecular, genomic and epidemiological level, for clinical decision-making in the management of these patients.

Bridget Marcellino, MD, PhD; Xiaobao Yang, PhD; H. Ümit Kaniskan, PhD; Alan Shih, MD, PhD; and colleagues

An MDM2 degrader for treatment of acute leukemias

Leukemia. 2022 Oct 29. PMID: 36309559

To more efficiently target MDM2 in acute myeloid leukemia (AML), Dr. Marcellino et al. developed and evaluated the MDM2 VHL-based degrader, MS3227. The PROteolysis TArgeting Chimera (PROTAC) MS3227 shows activity against AML pre-clinically and cooperates with other anti-leukemic therapies to target the MDM2-p53 pathway. These combination therapies have the potential to provide greater therapeutic potential and overcome resistance mechanisms when treating AML and myeloid malignancy patients.

The Liver Cancer Program will hold its annual “Updated Review of Clinical Management and Translational Science” on Friday, December 16.

8:30 am - 4:30 pm

Davis Auditorium

Leon & Norma Hess Center for Science and Medicine

Program

Register

TCI Seminar Series

December 6, Noon, Davis Auditorium

Kathryn O'Donnell, PhD

UT Southwestern Medical Center

"Regulation and Therapeutic Targeting of Cell Surface Proteins in Lung Cancer"

William Oh, MD, and Eimear Kenny, PhD, served on a panel at the Illumina Genomics Forum. Speakers included former President Barack Obama, Bill Gates, 23andMe co-founder and CEO Anne Wojcicki, tennis legend and cancer survivor Chris Evert, and American Cancer Society CEO Karen Knudsen.

Illumina Press Release

TCI is accepting applications from outstanding junior faculty MD, DO, or MD/PhD physician scientists conducting multidisciplinary translational research for the 2023 Paul Calabresi Award in Clinical Oncology Research (PCACOR).

The K12 Scholars Program offers awardees opportunities for mentored research, curricular activities, and a needs-based tailored education to prepare them to successfully compete for peer-reviewed research funding and to advance their knowledge, skills and capacity for clinically impactful cancer research.

TCI’s K12 leadership includes Nina Bhardwaj, MD, PhD; James Ferrara, MD; and Samir Parekh, MD.  

Application due date: January 15, 2023

Notification of awards will be made by April 1, 2023.

Funding will begin July 1, 2023.

See RFA for details.

Questions? Contact Laura Piraino laura.piraino@mssm.edu