October 2020
From TCI Director Dr. Ramon Parsons
As you will read in this issue, our faculty and staff have many accomplishments that are newsworthy and of scientific merit. Of particular note are a recent publication in Nature from Arvin Dar, an endowed professorship for Julio Aguirre-Ghiso, and a U54 grant for Fred Hirsch. As always, I am honored to serve with such talented colleagues and am very proud of the impact The Tisch Cancer Institute makes on developments in cancer research and therapies for patients.

Nature. 14 Sept 2020. PMID: 32927473

Dr. Dar reports in this paper on the mechanism of action of the clinically approved anticancer drug trametinib. Trametinib has been a mystery because of how it was discovered through what are called phenotypic screens. Using a variety of chemical biology approaches, Dr. Dar and his research team showed that the functional target of trametinib is unexpectedly a co-complex formed between the protein MEK and its scaffold KSR. Based on this, they created an improved analog, called trametiglue. This new compound displays unprecedented activity in preclinical models, and is able to overcome a common drug-resistance mechanism that has thus far limited the use of trametinib and similar drugs in RAS-driven cancers. RAS is the most frequently mutated human cancer gene, and despite its first discovery as an oncogene almost four decades ago, therapeutic options for RAS cancers remain significantly limited. The work in this paper opens an entirely new approach for tackling the RAS pathway that could lead to more efficacious and less toxic therapies in patients.

Dr. Dar is Associate Professor, Oncological Sciences and Pharmacological Sciences, and Associate Director of the Mount Sinai Center for Therapeutic Discovery.
Julio Aguirre-Ghiso, PhD, was named Mount Sinai Professor in Cancer Biology at the 2020 Convocation of the Icahn School of Medicine at Mount Sinai on October 1. Dr. Aguirre-Ghiso is Professor of Medicine (Hematology and Medical Oncology), Otolaryngology, and Oncological Sciences. He is Co-Leader of the Cancer Mechanisms Program at The Tisch Cancer Institute, Research Leader of the Metastasis Treatment Center, and Director of Head and Neck Cancer Basic Research in the Department of Otolaryngology. He is also a member of the Precision Immunology Institute and Black Family Stem Cell Institute. Dr. Aguirre-Ghiso has been conducting research on cancer metastasis at Mount Sinai for the past 12 years.

“Julio has led a highly successful independent laboratory that has made major discoveries that have established the paradigm for the mechanism of metastatic cancer cell dormancy. He is highly deserving of this endowed chair,” said Dr. Ramon Parsons.

“This endowed professorship will allow my lab to explore high-risk and high-gain science initiatives that over the years have fueled a change in our understanding of cancer biology and have led to tangible translational and clinical output,” said Dr. Aguirre-Ghiso.

In addition to thanking his family and numerous supporters and mentors at Mount Sinai, Dr. Aguirre-Ghiso acknowledged his trainees and lab members for carrying out the science and shaping his thinking, and he dedicated the endowed professorship to his mother, the first person to encourage him to pursue his love of science.

Fred R. Hirsch, MD, PhD, and Adolfo Garcia-Sastre, PhD, received a U54 award from the NCI to lead a Serological Sciences Network (SeroNet) Center of Excellence to study lung cancer patients’ vulnerability to developing SARS-CoV-2 infection. This is one of eight centers of excellence funded by the NCI as part of the SeroNet initiative, the nation’s largest coordinated effort to study immunology and SARS-CoV-2. (The Icahn School of Medicine is one of just four research institutions awarded subcontracts as part of the SeroNet initiative to develop serological assays to test for coronavirus antibodies and to conduct serosurveillance studies.)

“Our overall hypothesis is that lung cancer patients have a weaker antibody response to COVID-19 and that their lung tissue and tumor cells may play a role in their body’s response to infection, which could explain the aggressive course and high fatality rate that we’ve seen,” said Dr. Hirsch. “Our U54 Serologic Center will determine whether COVID-19 infection or vaccines will give similar antibody responses in patients with lung cancer compared to patients without lung cancer.” 

Others involved in the study include Mount Sinai researchers Rachel Brody, MD, PhD; Jorge Gomez, MD; Claudia Henschke, PhD, MD; Florian Krammer, PhD; Philip Mack, PhD; Emanuela Taioli, MD, PhD; and David Yankelevitz,MD; as well as researchers from the University of Texas Southwestern, University of Colorado, University of Maryland, and Vanderbilt University. 

Lewis Silverman, MD, was honored by the Myelodysplastic Syndrome Foundation with the Nobility of Science Award for his many years of dedicated services in providing leading research, drug approval, and outstanding care for patients diagnosed with Myelodysplastic Syndrome (MDS). 

In receiving the award, Dr. Silverman acknowledged his research team. “Without their dedication persistence, and resilience, our efforts would have never been as successful,” he said.

Dr. Silverman also thanked his patients “who have contributed enormously to the research effort, who have participated in clinical trials while battling such a difficult illness, and being unrelenting and unwavering both in their ability to battle MDS and make their contributions to research.”

John Levine, MD, has been elected to a major leadership role with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). He will serve as Vice Chair this year, followed by Chair Elect and Chair. BMT CTN conducts large multi-institutional clinical trials that address important issues in hematopoietic stem cell transplantation. It is funded through two divisions at the National Institutes of Health: the National Heart, Lung, and Blood Institute and the National Cancer Institute
James Manfredi, PhD, was appointed chairperson of the Tumor Cell Biology Study Section, Center for Scientific Review, National Institutes for Health, for a term running from July 1, 2020 through June 30, 2022. The Tumor Cell Biology Study Section reviews applications that focus on mechanisms of tumor cell metabolism and signal transduction that regulate or influence tumor phenotype, behavior, progression, and tumor-associated cachexia. Chairing this study section provides a unique opportunity to contribute to the national biomedical research effort.
Jose Javier Bravo-Cordero, PhD, was elected as a member of the board of the Metastasis Research Society, with a four-year term that began on
October 18.

Julio Aguirre-Ghiso, PhD, serves as President-elect.
Fred R. Hirsch, MD, PhD, was recognized for his landmark achievements in lung cancer at CURE®’s inaugural Lung Cancer Heroes Program on October 15.

“I have been very lucky to be in the right place in the right time,” Dr. Hirsch said of his career in lung cancer research when accepting his honor.

“While scientific and organization developments have been landmarks for Fred, his care for patients has always been in the center and, as a cancer survivor himself, he will always have that philosophy,” said Dr. Ramon Parsons, who nominated Dr. Hirsch for the award.

Three members of The Tisch Cancer Institute were honored with the
Jacobi Medallion Award on Oct. 6:

Kuan-lin Huang, PhD, has been awarded an R35 from the NCI for “Integrative Approaches for Identifying Causal Gene-Cell Type Pairs of Complex Disease.” The goal is to develop innovative methods to identify disease-associated gene-cell pairs by integrating large-scale bulk and single-cell molecular data of patient and cell cohorts. The resulting software can be applied to deconvolute the complex cell types and genetic alterations found across many cancer types to derive treatment hypotheses at high-resolution. 
Development of a Platform for Spatial Functional Genomics. His project will establish a first-of-its-kind platform for spatial functional genomics, which will enable broad phenotypic analysis of hundreds of genes in parallel within a tissue or tumor at cellular resolution and with spatial architecture preserved. This will greatly accelerate functional annotation of the genome and discovery of tissue and tumor biological control and thus transform efforts to uncover the intrinsic components of different diseases and facilitate development of drugs to treat these diseases.
The Federal Communications Commission’s Wireline Competition Bureau has awarded $923,487 to the Icahn School of Medicine at Mount Sinai for the COVID-19 Telehealth Program. The funds will be used for tablet computers and a remote monitoring platform license to ensure that vulnerable cancer patients across all New York City boroughs remain connected to oncology clinicians via telehealth services during the COVID-19 pandemic. Under the leadership of Cardinale Smith, MD, PhD, clinicians within each disease team are identifying eligible patients; devices will be given to patients when they are in the clinic or sent to them at their residence. The devices are expected to arrive by early November.
Julio Aguirre-Ghiso, PhD, in partnership with Jianlong Wang, PhD, at Columbia University, was awarded a Breast Cancer Research Program Breakthrough Award from the Department of Defense. Their research aims to decipher the stemness code conferred by pluripotency regulators in embryonic stem cells, as opposed to those in adult stem cells, to complement and unify the cancer stem cell concept for breast cancer metastasis.
Bassem Khalil, PhD, postdoctoral fellow in Dr. Aguirre-Ghiso’s lab, was awarded a Ruth L. Kirschstein Institutional National Research Service Award (T32) from the NIH. Dr. Khalil is investigating a small molecule that activates NR2F1, a nuclear receptor that is a key player in the dormancy induction pathway, and inhibits metastasis by activating a cell dormancy pathway. He is examining the underlying mechanisms and the potential therapeutic use of NR2F1 agonists to prevent metastasis.
Jose Javier Bravo-Cordero, PhD, was awarded an R01 grant from the NCI for “Defining the role of type III collagen and the collagen-binding receptor DDR1 in metastatic dormancy.” Dr. Bravo-Cordero will explore the hypothesis that dormant cancer cells can construct their own dormancy-supportive niche by remodeling and depositing a collagen III (COL III) extracellular matrix (ECM) that sustains their phenotype. The overall goals are to understand the role of the COL III ECM on the formation of dormancy-supportive niches and determine how the interaction with the COL III ECM through DDR1 regulates the dormancy-to-reactivation transition. Findings could inform identification of targets to prevent metastasis.
P30 Cancer Center Support Grant Administrative Supplements

  • The Association of Clonality with Age and Anal Precancer Recurrence in People Living with HIV. Principal Investigator: Paz Polak, PhD

  • The Role of HIV in the Microenvironment of Non-Small Cell Lung Cancer. Principal Investigator: Keith Sigel, MD; Co-Investigator: Paz Polak PhD

  • Identifying Immune Correlates of Disease Severity and Novel Immune Drivers of Pathogenicity to Target Patients with COVID-19. Principal Investigator: Miriam Merad, MD, PhD

  • Collaboration with Experimental Therapeutics Clinical Trials Network (ETCN) Through the Early Drug Development Opportunity Program (EDDOP). Principal Investigator: Karyn Goodman, MD, MS
Grant Opportunities from the

Application due date: December 1, 2020

Application due date: December 1, 2020

Application due date: February 1, 2021

Nature Reviews Cancer. 09 Sept 2020. PMID: 32908223

This review focuses on the role of hyperinsulinaemia in cancer. The authors discuss how endogenous hyperinsulinaemia develops in the setting of obesity and overnutrition, the epidemiology linking endogenous hyperinsulinaemia and cancer, the mechanisms through which insulin promotes cancer growth, and therapeutic strategies to reduce the tumor-promoting effects of insulin. They also address insulin-like growth factor 1 (IGF1) and the IGF1 receptor (IGF1R) as related to insulin and insulin receptor (INSR) signaling in hyperinsulinaemia-associated cancer.

Oncogene. 23 Oct 2020. PMID: 33097857

This study describes the mutational landscape of advanced hematocellular carcinoma (HCC) and identifies predictors of primary resistance to systemic therapies using circulating tumor DNA (ctDNA). It confirms the previous association between PI3K/MTOR pathway mutations and poor outcomes in patients receiving tyrosine kinase inhibitors (TKIs). Patients with mutations in the PI3K/MTOR pathway had significantly shorter progression free survival (PFS) than those without these mutations after TKIs, but not after immune checkpoint inhibition (CPI). WNT pathway mutations were not associated with PFS, overall survival, or objective response after CPI. The findings demonstrate the clinical utility of ctDNA analysis and its importance for future biomarker development in HCC, particularly in patients without available tissue samples.

Nature Communications. 9 Oct 2020. PMID: 33037222

In this genome-wide association study of 24,192 women, the researchers identified 31 novel mammographic density (MD) loci, tripling the number now known. The study findings reveal new genes for MD and breast cancer risk, and support the etiologic role of the nondense fatty area as well as dense tissue area and percent density as modifiable risk factors for breast cancer that provide potential for intervention.

Biology of Blood and Marrow Transplantation. 18 Aug 2020. PMID: 32818555

The impact of ruxolitinib, an oral JAK1/2 inhibitor approved for use in patients with intermediate and high-risk myelofibrosis (MF), on hematopoietic stem cell transplantation (HSCT) outcomes is largely unknown. This paper provides a review of published data to guide the management of patients with MF on ruxolitinib proceeding to HSCT. 
Deborah Doroshow, MD, PhD, presented at the 2020 Virtual Congress of the European Society for Medical Oncology (ESMO):

The study identified significant disruptions to routine cancer care, exacerbated by racial and ethnic barriers to telehealth visits and increased risk in vulnerable populations for COVID infection.

The study team included Matthew Galsky, MD; Sheena Bhalla, MD, Chief Fellow, Hematology and Medical Oncology; and multiple Hematology and Medical Oncology fellows and Internal Medicine residents.

Mount Sinai Liver Cancer Conference

Liver Cancer: Advances in Science and Clinical Management, December 11
Program Director: Josep Llovet, MD, PhD
Frontiers in Oncology
December 15, 12 noon
Guest presenter: David Tuveson, MD, PhD

Dr. Tuveson is a world-renowned physician-scientist whose basic and translational research focuses on the biology of pancreatic cancer and on identifying and testing in preclinical and clinical settings new approaches for diagnosing and treating the disease. He is the director of the Cold Spring Harbor Laboratory Cancer Center and chief scientist for the Lustgarten Foundation, the largest private funder of pancreatic cancer research. Dr. Tuveson is president-elect of the American Association for Cancer Research (AACR) and scientific editor of the AACR journal Cancer Discovery.
Natalie Lewis-Ross, Director of Operations and Human Resources at The Tisch Cancer Institute for the past 12 years, is retiring at the end of October. During her tenure, Natalie was instrumental in helping to create a strong workforce in support of TCI’s research, patient care, and educational missions.

Amina Dixon has been promoted to Administrative Director. She will oversee all Human Resource functions for TCI and the Division of Hematology and Medical Oncology. She will also provide administrative oversight for the Hematology and Medical Oncology Fellowship Training Program, and will handle facilities management and IT issues.

Milana Abramov has joined TCI as Administrative Manager. She will be responsible for faculty appointments, promotions, and credentialing, and will oversee the administrative staff who support TCI faculty. A former TCI employee, Milana was most recently the Office Manager for Hepatology Associates at NYU Langone Health.
Center of Excellence for Breast Cancer

The Center of Excellence (COE) for Breast Cancer, Elisa Port, MD, Director, officially launched in October, coinciding with Breast Cancer Awareness Month.

Every day in October, Mount Sinai's breast cancer faculty provided informational videos that were posted on social media.
View the videos here.
Multiple Myeloma Services in Chelsea

The Center of Excellence (COE) for Multiple Myeloma has expanded its outpatient clinical services at The Blavatnik Family – Chelsea Medical Center at Mount Sinai. Sundar Jagannath, MD, Director of the COE, now sees patients one day a week at the Blavatnik Center; Shambavi Richard, MD, and Joshua Richter, MD, Site Director of Myeloma Services at the Blavatnik Center, have been providing multiple myeloma services there for more than a year. This expansion of services offers patients the convenience of receiving multiple myeloma care at a downtown location in addition to The Ruttenberg Treatment Center at The Mount Sinai Hospital.
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.
  TCI Connections  is a monthly publication of The Tisch Cancer Institute
Ramon Parsons, MD, PhD, Director
Janet Aronson , Editor
Past issues of  TCI Connections  are available on the TCI website