May 2022

Carolina Rodriguez-Tirado, PhD; Alcina Rodrigues, MS; Jose Javier Bravo-Cordero, PhD; Maria Soledad Sosa, PhD; and colleagues

NR2F1 is a barrier to dissemination of early stage breast cancer cells 

Cancer Research. 2022 Apr 26. PMID: 35471456

Findings from this study show that the NR2F1 gene serves as a barrier to early dissemination of ductal carcinoma in situ, but that during early stages of breast cancer progression, HER2 suppresses NR2F1, allowing pre-cancerous cells to disseminate to other organs of the body—commonly the lungs, bones and brain—where they can lie dormant and later become cancerous. Understanding the mechanisms that allow pre-malignant cells to spread throughout the body may help identify patients at a higher risk for breast cancer relapse.

Press Release

Nina Bhardwaj, MD, PhD, received the 2022 Lifetime Achievement Award from the American Association of Indian Scientists in Cancer Research. This annual award is presented to an outstanding scientist who has made significant fundamental contributions to cancer research, with a lasting impact, and who has demonstrated a lifetime commitment to progress against cancer.

Award Recipients

Madhu Mazumdar, PhD, received the 2022 Elizabeth L. Scott Award from the Committee of Presidents of Statistical Societies. The award recognizes an individual who serves as an outstanding role model of leadership, promotes statistical careers for diverse trainees, mentors the next generation of statistical leaders, and excels in team science research. Dr. Mazumdar will deliver the E.L. Scott Lecture at the 2022 Joint Statistical Meeting in August in Washington, DC: "Biostatistical Methods and Team Science: Generating Evidence for Optimization of Clinical Practice."

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Carlos Cordon-Cardo, MD, PhD, will receive a 2022 Jacobi Medallion from the Mount Sinai Alumni Association and Icahn School of Medicine at Mount Sinai. The award ceremony will take place on June 21.

Faculty Council Awards, Icahn School of Medicine at Mount Sinai

The following were honored at the 2022 Faculty Council Awards Ceremony on May 4:

• Deborah Doroshow, MD, PhD, Hematology and Medical Oncology, Solomon Silver Award in Clinical Medicine
• Scott Friedman, MD, Pharmacological Sciences and Liver Diseases, Faculty Council Lifetime Achievement Award
• Rajwanth Veluswamy, MD, Hematology and Medical Oncology, Lamport Clinical Research Award
• Kristen Zeligs, MD, Gynecologic Oncology, Faculty Council Junior Award

Ashutosh Tewari, MD, was honored for his contributions in cancer research by the Society of American Asian Scientists in Cancer Research on April 10 at the organization’s annual meeting.

Article in India West Journal

Derek LeRoith, MD, PhD, who investigates the link between insulin and insulin-like growth factors and cancer, was selected to receive the 2022 Human Growth Foundation (HGF) Robert Blizzard Award in recognition of his significant contribution in the field of growth and growth disorders. The award will be presented on June 12 at the HGF Awards Gala in Atlanta.

Myron Schwartz, MD, was elected Vice-President of the International Society of Liver Surgeons. Also, Dr. Schwartz received the Community Service Award from the Chinese-American Medical Society on May 7. 

Constantinos Hadjipanayis, MD, PhD, was elected Secretary/Treasurer of the American Association of Neurological Surgeons/Congress of Neurological Surgeons Executive Committee for a two-year term; he will serve as Chair in 2024. 

Eirini P. Papapetrou, MD, PhD, was awarded funding from the AACR-MPM Oncology Charitable Foundation Transformative Cancer Research Grants Program for “G Protein Signaling as a Novel Target for Splicing Factor-mutant Cancers.” Dr. Papapetrou will investigate G⍺s as a therapeutic target and evaluate therapeutic interventions that inhibit signaling downstream of its long form (G⍺s-L) assessed by in vitro and in vivo functional assays using induced pluripotent stem cell model and primary myelodysplastic syndrome cells.

Lucas Ferrari de Andrade, PhD, received a U.S. Department of Defense grant to develop new immunotherapeutics for acute myeloid leukemia. The Ferrari de Andrade Laboratory previously developed an antibody that binds leukemia cells and alerts malignant transformation to the immune system; the antibody promotes recognition of leukemia cells by macrophages, which in turn phagocytose and destroy them. The lab also discovered that a histone deacetylase inhibitor, romidepsin, synergizes with the antibody to increase expression of the antigen. Dr. Ferrari de Andrade and team will now determine if the combination of these two molecules promotes macrophage-mediated immunity against human acute myeloid leukemia in pre-clinical models. 

Elena Ezhkova, PhD, received a Rare Cancer Research Program Idea Development Award from the U.S. Department of Defense for “Exploring Merkel Cell Stem Cells as Cells of Origin of Merkel Cell Carcinoma.” The goal is to generate a mouse model of Merkel cell carcinoma (MCC), an aggressive and deadly skin cancer for which there is no effective treatment, and which has a dismal survival rate.

Jian Jin, PhD, and Greg Wang, PhD, UNC Chapel Hill, received a five-year multiple-PI R01 grant from the National Cancer Institute to develop first-in-class WDR5 PROTACs as a novel and superior therapeutic strategy to pharmacological inhibition of protein-protein interactions between WDR5 and its binding partners for the treatment of MLL-rearranged leukemias, building on preliminary results published in Science Translational Medicine.

The Tisch Cancer Institute (TCI) Mouse Genetics Shared Resource Facility (MGSRF) provides TCI members with access to state-of-the-art facilities for the production of transgenic and knockout cancer models in mice, as well as related rodent embryology techniques.

The MGSRF produces transgenic mice by injection of DNA fragments into pronuclear stage single-cell mouse embryos, and assists laboratories with the production of targeted mutant lines of mice through the use of mouse embryonic stem (ES) cells or CRISPR/Cas9 gene editing.

In addition to the creation of novel mouse lines, the MGSRF assists TCI laboratories with the maintenance of existing lines through the cryopreservation of sperm, and with the import of novel lines from other institutions by recovering mice from cryopreserved embryos or sperm, live embryos, or through the use of IVF rederivation of individual males that are shipped to ISMMS. 

Recent enhancements include:

• CRISPR gene-editing by 2-cell homologous recombination CRISPR
• Easi-CRISPR with long single-stranded DNA templates
• Electroporation of CRISPR gene-editing reagents into mouse embryos

For more information, researchers can contact Kevin Kelley, PhD at 212-659-6866 or Jerry Edward Chipuk, PhD, Associate Director of Basic Science Shared Resources at TCI.

Other Shared Resources News

The Microscopy CoRE is assessing interest in a new Mica microscope.

Leica will offer demo sessions between May 10 and May 20.

Sign up here to attend a session in Annenberg 18-250.

The Mount Sinai Institute for Exposomic Research, one of the world’s leaders in the nascent field of exposomics, is home to two NIH-funded Human Health Exposure Analysis Resource (HHEAR) Lab Hubs that assess the exposome (health relevant environmental exposures), including carcinogens that underlie the gene-environment interactions in tumorigenesis, and the HHEAR Data Center. It is the largest NIH-funded exposomic research program. The Targeted Lab Hub measures panels of exposure biomarkers for known and suspected carcinogens (persistent organic pollutants, pesticides, trace elements and per-fluoryl alkyls). The Untargeted Lab Hub uses high resolution mass spectrometry to scan the exposome in biological specimens to discover thousands of chemicals that may be associated with cancer. The HHEAR Data Center houses computational and informatics support for statistical analysis of complex mixtures and exposomic data that are measured by the lab hubs. All NCI-funded population-based studies on cancer (e.g. epidemiologic, clinical populations, and randomized trials) and all NCI-funded studies that retain human samples are eligible to have their biospecimens analyzed by HHEAR at no cost for a wide range of environmental risk factors for cancer. 

For more information, contact Robert O. Wright, MD, MPH; Manish Arora, BDS, MPH, PhD, (Lab Directors); or Susan Teitelbaum, PhD (Data Center)

Learn more about HHEAR

Information at National Institute of Environmental Health Sciences

Congratulations to the following students who successfully defended their theses:



• James Carter, MD/PhD student mentored by Scott Friedman, MD

“Distinct Contributions of Protocadherin 7 in Chronic Liver Disease and Liver Cancer”

• Mary Duffy, PhD student mentored by Arvin Dar, PhD

“Targeting CTNNB1-mutant Hepatocellular Carcinoma with a Novel Kinase Inhibitor”

• Alex Real, MD/PhD student mentored by Arvin Dar, PhD

“Small Molecule Interactions Directed to the Scaffold Kinase Suppressor of Ras Modulate MAPK Signaling in Cancer”

• Ivan Reyes-Torres, PhD student mentored by Miriam Merad, MD, PhD

"The Role of TREM2 Signaling in Modulating Macrophage Molecular Phenotype and NK Cell Antitumor Immunity in Non Small Cell Lung Cancer”

• Joel Kim, MD/PhD student mentored by Miriam Merad, MD, PhD 

“Dissection of Macrophage Diversity in Hepatocellular Carcinoma Elucidates Molecular Correlates to a PD-1 Response”

Arthur Chow, student in the Dar Lab, won second place at the student/postdoc poster competition at the American Society for Pharmacology and Experimental Therapeutics annual meeting for his work on “An Antagonist of KSR-driven Adaptive Resistance to Clinical RAS-MAPK Inhibitors.”

Valerie Marallano, BS, PhD student in Cancer Biology in the Friedel Lab, received a 2022 Ruth L. Kirschstein Individual Predoctoral Fellowship Award (F31 - Diversity) from the National Institutes of Health for her project “Functional Analysis of Hypoxia-induced Genes in Promoting Malignant Growth of Glioblastoma.” Using mouse models and genetic engineering of patient brain tumor cells, Ms. Marallano will examine the role of hypoxia-induced genes in increasing invasiveness and treatment resistance of glioblastoma cells. 

Raphael Mattiuz, PhD, in the Merad Lab received the American Association for Cancer Research (AACR)-Astrazeneca Fellowship Award at the AACR Annual Meeting 2022 in April.

Philip Mack, PhD; Jorge Gomez, MD; Fred R. Hirsch, MD, PhD; and colleagues

Longitudinal COVID-19 vaccination-induced antibody responses and Omicron neutralization in patients with lung cancer

Cancer Cell. 2022 Apr 20.

This study found that the majority of patients with lung cancer mounted an adequate antibody titer in response to COVID-19 vaccination, but a subset (five percent) displayed a diminished or o response despite full vaccination as compared to healthy controls. The small fraction of lung cancer patients with absent antibody responses highlights the urgent need to identify characteristics underlying this effect and to investigate the potential benefits of booster vaccinations in this population.

Oren Becher, MD, and colleagues

A tumor suppressor role for EZH2 in diffuse midline glioma pathogenesis

Acta Neuropathologica Communications. 2022 Apr 8. PMID: 35395831



In this study, the first to elucidate the complex role of enhancer of zeste homolog 2 (EZH2) in diffuse midline glioma (DMG), Dr. Becher and colleagues demonstrate a tumor suppressor function for EZH2 using Ezh2 loss- and gain-of-function studies in H3WT DMG mouse models. Results suggest a potential tumor suppressive role for EZH2 in DMG and careful investigation of the use of EZH2 inhibitors in the clinic.

Scott Friedman, MD

Fighting cardiac fibrosis with CAR T cells

New England Journal of Medicine. 2022 Apr 21. PMID: 3543114

In this review, in the journal’s Clinical Implications of Basic Research series, Dr. Friedman addresses the potential of chimeric antigen receptor (CAR) T cells, originally developed to kill cancer cells, to clear fibrogenic, nonmalignant cells from the heart and liver.

Josep Llovet, MD; Augusto Villanueva, MD, PhD; and colleagues

Molecular pathogenesis and systemic therapies for hepatocellular carcinoma

Nature Cancer. 2022 Apr 28. PMID: 35484418

In this review, the authors discuss the molecular pathogenesis of hepatocellular carcinoma, molecular classes, and determinants of heterogeneity, and they analyze effective single-agent and combination systemic therapies involving immunotherapies as standard of care. They propose a flowchart of sequential therapies, explore mechanisms of resistance, and address the need for predictive biomarkers.

Parita Ratnani, MPH; Zachary Dovey, MBBS; Ashutosh Tewari, MBBS; and colleagues

Prostate MRI percentage tumor involvement or “PI-RADS percent” as a predictor of adverse surgical pathology

The Prostate. 2022 Apr 19. PMID: 35437769



This study on a cohort of 557 patients assesses magnetic resonance imaging prostate percent tumor involvement or "PI-RADs percent" as a predictor of adverse pathology (AP) after surgery for localized prostate cancer. Increasing PI-RADS percent—which outperforms PSAD, a more commonly used clinical tool—was associated with a higher risk of AP. Using PIRADs percent to predict AP for presurgical patients may help risk stratification, and for low and low volume intermediate risk patients, may influence treatment decisions.

Andrew Srisuwananukorn, MD, is the recipient of the Paul Carbone, MD Fellowship Award—a research grant that aims to promote excellence in clinical trials leading to improvements in cancer care—from ECOG-ACRIN Cancer Research Group. The award is given each year to one outstanding senior oncology or hematology research fellow at a member institution.

Caitlin Carr, MD, senior fellow in Gynecologic Oncology, was honored at the Society of Gynecologic Oncology (SGO) 2022 Annual Meeting on Women’s Cancer with the SGO 2021 Annual Meeting Best Oral Poster award for “Outcomes of Gynecologic Oncology Patients at an Epicenter of the COVID-19 Pandemic.”

Presentations from the Llovet Lab at the AACR Special Conference: Advances in the Pathogenesis and Molecular Therapies of Liver Cancer, Josep Llovet, MD, Co-chair:

• Marta Pique: “PMEPA1 Has an Oncogenic Role in the Context of TGF-β Signaling in Hepatocellular Carcinoma”
• Sarah Cappuyns: "Pre-treatment Immune Cell Composition and Checkpoint Ligand Expression Define the Response to Immunotherapy in Advanced HCC: A Study Using Single-cell Sequencing"
• Jordi Abrilfornaguera: “Identification of IGF2 as Genomic Driver and Actionable Therapeutic Target in Hepatoblastoma”

Upcoming Presentations

TCI Seminar Series

Tuesday, May 17, Noon

Nikhil Joshi, PhD, Yale School of Medicine

"Investigating Anti-Cancer T Cell Responses with Engineered Models"

Tuesday, May 24, Noon

Scott L. Friedman, MD

"Fat, Fibrosis, and Liver Cancer in Non-Alcoholic Steatohepatitis (NASH)"

Special Seminar

Veronica Torrano, PhD

University of the Basque Country

Monday, May 23, Noon

Hess Seminar Room B

"Deciphering the Essence of Prostate Cancer Aggressiveness: From Metabolism to ECM Deregulation"

Community Outreach and Engagement at The Tisch Cancer Institute (TCI) will hold its Spring Retreat, Q&A with Leaders in Cancer Care, May 16, 2022, 1-4 pm.

Register

View Flyer

Watch the video from the ribbon cutting ceremony for the Mobile Prostate Cancer Screening van.