Julio Aguirre-Ghiso, PhD, is a Professor at the Icahn School of Medicine at Mount Sinai in the Division of Hematology and Oncology in the Departments of Medicine, Otolaryngology, and Oncological Sciences; the Research Leader of the Metastasis Treatment Center and Co-leader of the Cancer Mechanisms Program at The Tisch Cancer Institute, an NCI-designated center, and Director of Head and Neck Cancer Basic Research in the Department of Otolaryngology. He focuses on one of the major challenges faced by physicians: prevention and treatment of metastasis, which is the main reason for cancer mortality. Cancer patients presumed cured after primary tumor removal and therapy can carry non-proliferating ‘dormant’ disseminated tumor cells (DTCs) for years before reactivating to form incurable metastasis. Dr. Aguirre-Ghiso’s work focuses on understanding the biology of residual cancer cells that persist in a dormant state after initial therapy. His team led a paradigm shift revealing novel cancer biology that diverges from the notion that cancer is perpetually proliferating. They discovered that reciprocal crosstalk between DTCs and the microenvironment regulates the inter-conversion between dormancy and proliferation. This knowledge will allow targeting minimal residual disease before it becomes clinically detectable, and thus preventing recurrences.

Ongoing research interests include:

• Exploring mechanisms controlling residual cancer dormancy
• Researching approaches to target dormant cancer cells
• Identifying markers to determine whether disseminated disease cells are dormant or active

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Emily Bernstein, PhD, is a Professor of Oncological Sciences and Dermatology at the Icahn School of Medicine at Mount Sinai and co-leader of the Cancer Mechanisms Program of The Tisch Cancer Institute, an NCI-designated center. She also organizes numerous epigenetics events including Mount Sinai’s Chromatin Club. Her team studies epigenetic mechanisms underlying normal development and cancer with a focus on histone variant proteins that replace canonical histones within the nucleosome core particle. Histone variants are specialized in function and represent an important layer of regulation to diversify the structural characteristics and functional outputs of chromatin. Her laboratory discovered a key role for H2A histone variants such as macroH2A and H2A.Z in melanoma malignancy and reprogramming towards pluripotency.

Ongoing research interests include:

• Investigating histone variant-deficient mice in normal development, stem cell populations, and tumor initiation/progression
• Understanding the role of the epigenome and non-coding DNA elements in cancer progression and drug resistance
• Modeling pediatric cancer mutations in chromatin factors by directed differentiation protocols of human pluripotent stem cells

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Elena Ezhkova, PhD, is an Associate Professor in the Cell, Developmental, and Regenerative Biology Department. Her laboratory implements an array of powerful cellular and high-throughput molecular biology tools to dissect how epigenetic gene regulators, specifically the polycomb repressive complexes 1 and 2 (PRC1 and PRC2), play a role in cell fate determination, homeostasis, and regeneration. Her lab has recently showed that PRC1 functions both as a transcriptional repressor and as a transcriptional activator during skin development. Importantly, PRC1-mediated gene activating functions are critical for hair follicle development and for the establishment of the adult bulge stem cell compartment. Identification of these molecular mechanisms that control cell fate determination, commitment, and differentiation aids in expanding our understanding of tissue development and the progression of various tissue disorders, including cancer. 

Ongoing research interests include:

• Uncovering the molecular mechanism of PRC-mediated gene regulation in skin development, homeostasis, and regeneration
• Dissecting the canonical and non-canonical PRC function in different epithelial tissues, including skin and oral epithelia
• Uncovering the molecular mechanisms controlling Merkel cell development and maintenance and Merkel cell carcinoma formation

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Saghi Ghaffari, MD, PhD, is a Professor of Cell, Developmental, and Regenerative Biology and a member of The Tisch Cancer Institute. Her lab studies mechanisms that sustain blood forming stem and progenitor cells (HSPCs) throughout life and that are perturbed in disease. Her team is particularly interested in programs that maintain quiescence of blood-forming stem cells, a property that determines the potency and overall regenerative capacity of adult stem cells and that is lost with age. Quiescence is also a mechanism by which malignant stem cells resist therapy. To attain this goal, the Ghaffari Laboratory has been investigating metabolic and mitochondrial-related programs and organelle communications in young and aged HSPCs. The Ghaffari lab uses a variety of approaches, including various omics, super resolution imaging, and gene modulation technology combined with genetically modified mouse models and human cells to address these questions.

Ongoing research interests include:

• Investigating mechanisms that control mitochondria-lysosome communication in normal mouse and human hematopoietic stem cells (HSCs) in aged HSCs and in leukemic stem cells
• Exploring transcriptional and epigenetic programs that regulate organelle biogenesis in HSPCs and their alteration with age
• Investigating metabolic and redox regulation of erythroid cell maturation and identifying mechanisms and components of mitochondria-nucleus communication during this process
• Elucidating mechanisms of apoptosis in beta-thalassemia

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Ernesto Guccione, PhD, is an Associate Professor of Oncological Sciences, and Pharmacological Sciences at the Icahn School of Medicine at Mount Sinai. His team studies transcriptional and post-transcriptional mechanisms regulating development and cancer with a focus on mammalian protein methyltransferases and the function of alternative splicing. The team uses biochemistry, mouse models, next generation sequencing and splice switching antisense oligonucleotide (AON)-based approaches to understand the molecular mechanisms of action of candidate PMTs or specific isoforms. The range of techniques and approaches used in the lab has allowed researchers to characterize the mechanism of action of specific PMTs (e.g., PRMT5 and PRDM15) or oncogenic isoforms (e.g., MDM4l/s), which are of great interest for their clinical applications.

Ongoing research interests include:

• Investigating the role of PRMTs and PRDMs in normal development, stem cell populations, and tumor initiation/progression
• Using AON-based approaches to uncover the function of specific alternative splicing isoforms
• Exploring use of pharmacogenomic approaches to identify new therapies for hematological and solid tumors

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Sarah E. Millar, PhD, is Director of the Black Family Stem Cell Institute, and Lillian and Henry M. Stratton Professorial Chair in the Departments of Cell, Developmental, and Regenerative Biology, and Dermatology at the Icahn School of Medicine at Mount Sinai. Understanding the molecular and cellular mechanisms regulating the development, patterning, and postnatal renewal of the skin and ectodermal appendage organs such as hair follicles, teeth, and taste papillae, and identifying stem and progenitor cell populations in these organs, is critical for developing new therapies to accelerate wound healing, treat hair loss diseases, repair or replace diseased teeth, and ameliorate taste dysfunction. Research in the Millar Laboratory focuses on cell-cell signaling and epigenetic mechanisms that underlie these processes. In published research, researchers identified Wnt/beta-catenin signaling as a key pathway required for initiating the formation of ectodermal appendages from multipotent cells in mammalian embryos, and in controlling development and patterning of haired versus hairy skin. By analyzing genetic mouse models and tissues from human patients carrying mutations in the WNT10A gene, we showed that Wnt signaling plays a key role in regulating the functions of a wide variety of adult epithelial stem cells, as well as in controlling specialized differentiation programs in palmoplantar skin. We have also identified critical functions for epigenetic regulators including micro-RNAs and chromatin modifiers in skin development and regeneration.

Ongoing research interests include:

• Investigating mechanisms that cause ectodermal dysplasia in patients with mutations in the WNT10A gene, and testing potential therapeutic strategies
• Determining the mechanisms that underlie the formation and maintenance of hairy versus hairless skin and regulate hair patterning
• Delineating the functions of histone deacetylase chromatin modifiers in skin development, stem cells, and cancer
• Identifying pioneer transcription factors that control development and stem cell activity in skin and oral epithelia

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Eirini Papapetrou, MD, PhD, is an Associate Professor of Oncological Sciences, Hematology, and Medical Oncology at the Icahn School of Medicine at Mount Sinai; and Associate Director of the Pluripotent Stem Cell Engineering Core. Her laboratory pioneered the modeling of blood cancers with human-induced pluripotent stem cell (iPSC). Specifically, her lab developed the first iPSC models of myeloid malignancies, including myelodysplastic syndromes and acute myeloid leukemia by reprogramming patient cells and by correcting and introducing mutations using CRISPR/Cas9-mediated gene editing. Dr. Papapetrou’s research program combines techniques and principles from stem cell research, cancer biology, and hematopoiesis with the goal of understanding disease mechanisms and identifying new therapeutic targets for hematologic malignancies. The unifying theme of the lab’s projects is the creation of genetically precise isogenic iPSC models of myeloid cancers and exploitation of the unique capabilities they offer for genotype-to-phenotype studies, interrogation of the effects of oncogenic mutations with integrative genomics analyses in a faithful cellular and genomic environment and genetic (CRISPR), and small molecule screens for drug repurposing or drug discovery. Dr. Papapetrou is the recipient of several awards, including the American Society of Gene and Cell Therapy Outstanding New Investigator Award, Damon Runyon-Rachleff Innovation Award, American Society of Hematology Scholar Award, Pershing Square Sohn Prize, and Leukemia and Lymphoma Society Scholar award, among others. She is an elected member of the American Society for Clinical Investigation.

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Alexander M. Tsankov, PhD, is an Assistant Professor in Genetics and Genomic Sciences at Icahn School of Medicine at Mount Sinai. He completed his PhD in electrical engineering and computer science at MIT and his postdoctoral training at the Broad Institute and Harvard University (Alex Meissner and Aviv Regev’s lab). The Tsankov lab overall vision is to use genomics to build data-driven, predictive models that improve diagnosis, find new drug-able pathways, and personalize treatment of patients with lung cancer and respiratory diseases. The lab specializes in next generation sequencing (NGS) technologies (e.g. single-cell transcriptomic, epigenomic, and spatial data) and computational analysis with the goal of unraveling how the underlying regulatory mechanisms, cell-cell interactions, and regenerative lineages have changed in lung disease compared to normal lung tissue homeostasis.

Ongoing research interests include:

• Using single-cell technologies to reconstruct the regenerative lineages in the human lung and to understand how these have been hijacked in cancer or altered in lung disease
• Investigating cell-cell interactions and their role on lung regeneration, disease progression, and immunosuppression.
• Dissecting the cell-type specific regulatory mechanisms underlying normal lung homeostasis and changes that arise in respiratory disease and lung cancer

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