Black Family Stem Cell Institute

Genomics

The growing application of multi-omics data in stem cell biology has facilitated a broad spectrum of basic and translational research.

The Black Family Stem Cell Institute has significant focus on creating and leveraging molecular assays to harness various layers of genetic, chromatin accessibility, proteomic, and epigenetic data in deciphering factors that differentiate pathogenesis from normal cellular development and function for basic discovery and translational research.  Using this data to reveal which cellular niches and mechanisms in complex primary tissues drive disease or resilience creates a feedback loop for translation of multi-omics data to apply stem cell models for high throughput validation of downstream regenerative and therapeutic potential. 

Discovering and associating gene specific transcriptional regulation of each cellular system informs the commitment of stem cell models in our effort to combine higher resolution multi-omics with basic and applied stem cell biology. From systematically modeling individual diseases in stem cells to testing perturbations induced using gene editing strategies for understanding complex pathologies to developing cancer therapy, regenerative, and personalized approaches, we are collectively generating and using genetic data to build the future of stem cell medicine at Icahn School of Medicine at Mount Sinai and beyond.

Investigators with a major focus in genomics approaches in stem cell research include:

Emily Bernstein, PhD

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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Kristen Brennand, PhD

Kristen Brennand, PhD, is an Associate Professor of Genetics and Genomics, Neuroscience, and Psychiatry at the Icahn School of Medicine at Mount Sinai. She trained in developmental and stem cell biology at Harvard University and in neuroscience during her postdoctoral studies at the Salk Institute for Biological Studies. By blending expertise in stem cell biology and neurobiology, she has pioneered a new approach to study psychiatric disease. By developing a G16 based model for the study of predisposition to neuropsychiatric disease, and combining it with CRISPR-based genomic engineering, the Brennand Laboratory has established a new approach by which to systematically test the impact of causal variants in human cells. The future of psychiatry requires a model of precision medicine, in which doctors consider how the patient’s genetic variants—and the many interactions among them—affect disease course and treatment response before prescribing any medication.

Ongoing research interests include:

  • Understanding the genetic mechanisms underlying schizophrenia
  • Developing personalized screening platforms to identify new therapeutics for the treatment of this debilitating disorder

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Elena Ezhkova, PhD

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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Ernesto Guccione, PhD

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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Eirini Papapetrou, MD, PhD

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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Michael Rendl

Michael Rendl, MD, is a Professor of Cell, Developmental, and Regenerative Biology and Dermatology at the Icahn School of Medicine at Mount Sinai; Director of the NYSTEM Training Program in Stem Cell Biology; and Associate Director of the Black Family Stem Cell Institute. His team studies the formation and function of stem cell niches, using hair follicle formation during skin development and adult hair growth and regeneration as a model system. Dermal papilla (DP) cells are specialized mesenchymal niche cells that instruct hair follicle stem cells and progenitors. His laboratory discovered embryonic DP precursors, defined molecular signatures of embryonic and mature DP cells, and established the essential roles of Wnt signaling and the transcription factor Sox2 for DP functions. The lab has uncovered the DP-related dermal sheath (DS) as a key niche component for hair cycle progression and progenitor pruning, essential for the next wave of stem cell activation. Overall, insights from these studies reveal mechanisms on how stem cell niches function and provide a platform for developing hair regenerative therapies.

Ongoing research interests include:

  • Understanding the molecular controls that regulate DP niche fate and function
  • Investigating DP signals that regulate stem cell and progenitor functions
  • Dissecting DS cellular and molecular mechanisms of hair cycle regulation

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Robert Sebra, PhD

Robert Sebra, PhD, is an Associate Professor in the Department of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai and Director of Technology Development and the Genomics Core Facility for the Icahn Institute for Data Science and Genomic Technology. His research lab centers on creating and applying bulk and single cell molecular methods to generate highly resolved data using genomics technology for variant discovery and annotation. This research integrates single molecular and cellular genomics data with assays to assess chromatin accessibility, proteomics, and epigenetics data to decipher factors of pathogenesis versus normal cellular functions. Determining which cellular niches and mechanisms in complex primary tissues drive disease or resilience facilitates translation of functional genomics data using model systems for screening possible downstream regenerative and therapeutic potential using high throughput methods.

Ongoing research interests include:

  • Developing novel molecular methods and genome sequencing technologies
  • Advancing high-throughput functional genomics
  • Exploring whole genome and repeat content characterization for disease association
  • Analyzing surveillance and genomic characterization of pathogen transmission
  • Using genomics to temporally characterize development and pathogenesis
  • Translating genomic data in various oncologic diseases including gynecologic and breast cancers

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Alexander M. Tsankov

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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