Message from the Director
Dear TCI Community,
 
The holiday season is a good time to reflect on what we do and reaffirm our mission: to advance basic, clinical and population health cancer research, so as to prevent cancer in healthy individuals and improve the lives of cancer patients and their families in our diverse communities. 
 
Working collaboratively, all of us, in every capacity— faculty, trainees, clinical and support staff —contribute to the renowned excellence of our cancer program, as evidenced by our nine competitively-scored R01 submissions and recent publications in high impact journals including Nature , Cancer Cell , and Cancer Discovery . In addition, the accrual for our therapeutic clinical trials is expected to exceed last year’s total. I extend my heartfelt thanks to everyone.
 
While we have so many recent accomplishments worthy of mention, I would like to highlight just a few.
 
In September, we submitted an application to the National Cancer Institute for renewal of our P30 Cancer Center Support Grant (CCSG) for continuation as an NCI-designated cancer center . The extraordinary efforts of all involved resulted in a thoughtful, comprehensive, and sound proposal that reported on progress since the previous application in 2014 and presented future directions. As far as what is new in the grant application, we are:


These additions and enhancements support our CCSG research programs in Cancer Mechanisms, Cancer Immunology, and Cancer Prevention and Control. Next steps in the grant application process include a meeting of our External Advisory Board in early January and a site visit from NCI reviewers shortly thereafter. I fully expect a favorable review with renewed funding.

In August, we established the Center of Excellence for Bladder Cancer , followed by the Center of Excellence for Multiple Myeloma in September. Additional centers of excellence—for lung cancer, breast cancer, prostate cancer, head and neck cancer, liver cancer, and adult blood cancers and myeloid disorders—are slated to launch in the near future.
 
In March, we initiated a quarterly e-newsletter that highlights our translational research and clinical advancements. The newsletter goes to more than 17,000 cancer doctors across the country with the goals of informing and raising awareness.
 
Finally, I am very pleased to recognize our outstanding representation at the 2019 annual December meeting of the American Society of Hematology (ASH) with 11 oral presentations and 28 poster presentations, as well as an oral presentation at the prestigious Plenary Scientific Session. View the full list of presentations .
 
With best wishes for the holiday season,
Ramon Parsons, MD, PhD
Director, The Tisch Cancer Institute
HONORS, AWARDS, GRANTS
2019 Tisch Cancer Institute Developmental Fund Awards
Our NCI Cancer Center Support Grant funds  The Tisch Cancer Institute Developmental Funds Awards, designed to support pilot projects that focus on translational and collaborative research between TCI cancer research programs . This year, the review committee, led by Stuart Aaronson, MD, considered eight applications. 

Congratulations to the two awardees selected for funding at $50K:

Alice Kamphorst, PhD (Cancer Immunology) & Thomas Marron, MD, PhD (Cancer Immunology, Cancer Clinical Investigation) – Identification of PD-1+ CD8 T Cells That Respond to Immunotherapy in Hepatocellular Carcinoma

Brian Brown, PhD (Cancer Immunology) & Poulikos Poulikakos, PhD (Cancer Mechanisms, Cancer Clinical Investigation) – Targeting Dual Functions of SHP2 for Direct Tumor Control and Enhancing Cancer Immunity

The next round of funding opportunity will be announced in early spring of 2020. 
Excellence in Physician Communications
Congratulations to Emily Gallagher, MD, PhD , and Constantinos Hadjipanayis, MD, PhD , recipients of the 2019 Cullman Family Award for Excellence in Physician Communications. The annual award, established in 2016 , honors practitioners who demonstrate exceptional communication in clinical practice, as reported via the Centers for Medicare and Medicaid Services’ Clinician and Group Consumer Assessment of Healthcare Providers and Systems (CG CAHPS) patient experience survey .
 
Dr. Gallagher is Assistant Professor of Medicine, Division of Endocrinology, Diabetes and Bone Disease. She specializes in the treatment of endocrine complications of oncology treatments. Dr. Hadjipanayis is Professor of Neurosurgery and Oncological Sciences. He is the Site Chair of the Department of Neurosurgery for the Mount Sinai Downtown Network, Director of Neurosurgical Oncology for the Mount Sinai Health System, and Director of the Brain Tumor Nanotechnology Laboratory for The Tisch Cancer Institute.
Lung Cancer Mentorship Award
Fred Hirsch, MD, PhD , was honored for his mentorship of lung cancer investigators by the International Association for the Study of Lung Cancer (IASLC), Latin America Group, at the 2019 Latin America Conference on Lung Cancer , held October 17-19 in Mexico City. The IASLC is the only global network dedicated to the study and eradication of lung cancer and other thoracic malignancies.
 
A member of IASLC for more than 40 years, Dr. Hirsch served as CEO from 2013 to 2018. Under his leadership, membership doubled, and the Journal of Thoracic Oncology experienced tremendous impact factor growth.
 
Dr. Hirsh is Executive Director of the Center for Thoracic Oncology and Associate Director of Biomarker Discovery at TCI.
The 2019 GE Liver Junior Scientist Award
Amaija Lujambio, PhD , received the 2019 GE Liver Junior Scientist award from Gene Expression, The Journal of Liver Research . The award was presented by Paul Monga, MD , Editor-in-Chief of the journal and Director of the Pittsburgh Liver Research Center , in conjunction with The Liver Meeting 2019 of the American Association for the Study of Liver Disease
Outstanding Abstract Achievement Award
Hrishi Srinagesh , 4 th year MD/MSCR student in the laboratory of James Ferrara, MD , received an Outstanding Abstract Achievement Award from the American Society of Hematology (ASH).

Mr. Srinagesh had the highest scoring abstract in the medical student category. He received the award at a special ceremony on December 7 at the annual ASH meeting , and made an oral presentation of his research, The MAGIC Algorithm Probability (MAP): A Novel Laboratory Biomarker for the Response to Treatment of Acute Graft-Versus-Host Disease , on December 8.
Dysregulated iron metabolism plays a pivotal role in
polycythemia vera
Yelena Z. Ginzburg, MD, Associate Professor of Medicine, Hematology and Medical Oncology, is one of just seven recipients of highly competitive research funding from the MPN Challenge Grant program , a partnership between the MPN (myeloproliferative diseases) Research Foundation and the Leukemia & Lymphoma Society. Dr. Ginzburg’s project, “Dysregulated Iron Metabolism Plays a Pivotal Role in Polycythemia Vera ,” aims to investigate how iron deficiency develops in polycythemia vera, how erythropoiesis persists at a high rate despite iron deficiency, whether iron metabolism is differently regulated in JAK2 mutated erythroblasts, and if JAK2 mutant bone marrow cells exhibit a competitive advantage during transplants. 
Lineage Heterogeneity and Plasticity in Lung Cancer
Hideo Watanabe, MD, PhD , was awarded R01 grant funding from the NCI for “Lineage Heterogeneity and Plasticity in Lung Cancer.”

With this grant funding, Dr. Watanabe and his team aim to improve the precision of lung cancer diagnostics and therapeutics by investigating the roles of novel lineage factors that define unique subgroups. By determining the heterogeneity and dynamics of lineage states at a single cell level, they aim to understand how lineage can switch within a tumor. They will test their hypothesis that the degree of heterogeneity correlates with the plasticity of the tumor and aggressive tumor behaviors. Results will enable them to evaluate the potential of inducing transdifferentiation as a therapeutic strategy.
Grant Opportunities

R35 opportunities with approaching deadlines:

 


For investigators within the first seven years of their faculty appointment.
Letter of Intent due date: December 15, 2019
 
Nurses are invited to submit innovative ideas aimed at improving oncology care for up to $100,000 in grant funding. Submission deadline: February 7, 2020
New Shared Resources

New equipment is now available through the Department of Oncological Sciences’ shared resources:
 


PUBLICATIONS
ATRX In-frame fusion neuroblastoma is sensitive to EZH2 inhibition via modulation of neuronal gene signatures


ATRX (Alpha Thalassemia/Mental Retardation, X-linked) is an epigenetic regulator mutated in pediatric and adult tumors. However, the consequences of ATRX alterations in cancer and on the epigenome remain ill defined. Focusing on the large structural variations of ATRX in neuroblastoma (NB), the researchers find that the consequent in-frame fusion (IFF) proteins lacking key chromatin-binding modules are altered in their genomic binding. ATRX IFFs localize to active promoters, notably that of REST, which encodes a neuronal transcriptional repressor. REST depletion and inhibition of EZH2 promote derepression of neuronal genes and cell death, suggesting cooperative pathways for silencing neuronal differentiation in ATRX IFF NB. These studies support EZH2 inhibitors as a therapeutic strategy to treat ATRX IFF NB patients, for which targeted treatment options are currently lacking. 
Structural insights into mutagenicity of aniticancer nucleoside analog cytarabine during replication by DNA polymerase η


Cytarabine (AraC) is the mainstay chemotherapy for acute myeloid leukemia (AML). While initial treatment with AraC is usually successful, most AML patients tend to relapse, and AraC treatment-induced mutagenesis may contribute to the development of chemo-resistant leukemic clones. The researchers show that whereas the high-fidelity replicative polymerase Polδ is blocked in the replication of AraC, the lower-fidelity translesion DNA synthesis (TLS) polymerase Polη is capable of promoting AraC induced mutations during chemotherapy. To see how Polη promotes mutations, the researchers determined high-resolution crystal structures of human Polη with template AraC. Taken together, the structures provide a novel basis for the ability of Polη to promote AraC induced mutagenesis in relapsed AML patients.
Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery


While gene expression can be activated or suppressed using CRISPR--Cas9 systems, tools that enable dose-dependent activation of gene expression without the use of exogenous transcription regulatory proteins are lacking. This article reports on chemical epigenetic modifiers (CEMs) designed to activate the expression of target genes by recruiting components of the endogenous chromatin-activating machinery, eliminating the need for exogenous transcriptional activators. The researchers show that CEMs upregulate gene expression at target endogenous loci up to 20-fold or more depending on the gene. They also demonstrate dose-dependent control of transcriptional activation, function across multiple diverse genes, reversibility of CEM activity, and specificity of best-in-class CEM across the genome.
Textures of the tumour microenvironment 


This review discusses how intravital microscopy has shed light into the dynamic nature of the tumor microenvironment (TME), revealing structural details of both tumor cells and other TME co-habitants  in vivo; how these cells communicate with each other; and how they are organized in three-dimensional space to orchestrate tumor growth, invasion, dissemination and metastasis. The biology uncovered by imaging tumors in vivo holds promise in finding targets that can stop cancer spread by targeting the ‘textures’ of the TME.
Recent trends in squamous cell carcinoma of the anus incidence and mortality in the United States, 2001-2015


This study is the first to characterize and systematically compare contemporary national squamous cell carcinoma of the anus (SCCA) incidence trends by stage at diagnosis, birth year, and mortality. The data revealed a rise in SCCA incidence, particularly advanced stage disease, and a similar rise in mortality, suggesting the rise in SCCA incidence rates is real and not driven by increased screening in some populations. Dramatic increases in SCCA incidence were noted particularly in elderly women and young Black men. Findings call for future studies to identify reasons for the increase in SCCA incidence and mortality and improved prevention strategies.
Disparities in surgery for early-stage cancer: the impact of refusal


This study, which examined whether refusal of recommended surgical interventions might contribute to disparities in treatment, reports that more vulnerable patients are at higher risk of refusing recommended surgery and that this decision negatively impacts their survival. Patients refusing surgery were at increased risk of death compared to patients who underwent surgery.
EDUCATION
Call for Mentors
The following opportunities are available for faculty to mentor students in basic science cancer research through the TCI Cancer Research Career Enhancement and Related Activities Core :

  • TCI Medical Student Research Fellowship (aka TCI Scholars)


If interested, please complete the TCI Education and Training form.


For students interested in applying for a TCI Medical Student Research Fellowship:
The application period opens in January and runs through March 16, 2020. The fellowship provides summer research stipends for rising second-year medical students at the Icahn School of Medicine at Mount Sinai who have not had extensive research experience to conduct original cancer research under the tutelage of a faculty member. Additional information will be announced and can be found at the TCI Training and Education website.
EVENTS
Oral Presentations at ASH
An abstract from the laboratory of Yelena Z. Ginzburg, MD , was selected for oral presentation at the Plenary Scientific Session at the annual meeting of the American Society of Hematology (ASH) on December 8. Melanie Castro-Mollo, MD, currently a master’s degree student in the lab, presented their work: Erythroferrone regulated bone remodeling in β-thalassemia , conducted in collaboration with Mone Zaidi, MD, PhD . The Plenary Scientific Session at ASH features the highest-caliber abstracts selected from among thousands submitted.
The Future of Cancer Care: From Discovery to Delivery
World Congress of Obstetrics and Gynecology
Michail Shafir, MD, MPH, Clinical Professor of Surgery and Oncological Sciences, presented the keynote lecture on ovarian carcinoid/neuroendocrine tumors at the World Congress of Obstetrics and Gynecology in Madrid, Oct. 7 - 9. Liane Deligdisch, MD, Professor of Pathology and Professor of Obstetrics, Gynecology and Reproductive Science, presented on endometrial cancer.
ASCO Annual Meeting, May 29-June 2
Abstract submission deadline:
February 11
Cancer-related Seminars and Events
Cancer-related seminars and events are posted on the Mount Sinai Health System online calendar. Remember to check the calendar periodically for updates and additions.
 
  • The TCI Seminar Series, focused on basic research, takes place every Tuesday at noon. The series includes talks from external and internal faculty members and postdoctoral presentations, as well as the quarterly TCI Frontiers in Oncology lecture.
 
  • TCI Translational Oncology Series takes place on Fridays at noon. One Friday each month features the Clinical Trials Science Meeting.
 
  • Hematology and Medical Oncology Grand Rounds take place on Thursdays at 8:30 am.

  • Cancer Biostatistics Walk-In Clinic takes place on Wednesdays at 1 pm.

  • Molecular Tumor Board takes place the second Friday of each month.
MOUNT SINAI CANCER IN THE NEWS - CLICK HERE
Do you have news for the next issue of    TCI Connections  

Please send to  Janet.Aronson@mountsinai.org   

Remember to share  breaking news  and  high impact news  that might be appropriate for media coverage with Marlene Naanes 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. Marlene.Naanes@mountsinai.org  , 929-237-5802
Corrections to the October issue:
  1.  Dr. Sieh’s first name was misspelled. The correct spelling is Weiva. Weiva Sieh, MD, PhD, MS
  2.  The title of Dr. Hirsch’s endowed professorship was incorrect. The correct title is Joe Lowe and Louis Price Professor of Medicine. Fred R. Hirsch, MD, PhD
    TCI Connections     is a monthly publication of The Tisch Cancer Institute.
Ramon Parsons, MD, PhD, Director
Co-editors: Janet Aronson and Rhaisili Rosario
Past issues of    TCI Connections    are available on the TCI website.