Dr. Bernstein is a Professor of Oncological Sciences and Dermatology at Mount Sinai School of Medicine in New York City. She performed her thesis research in the laboratory of Dr. Gregory Hannon at Cold Spring Harbor Laboratory with a PhD from Stony Brook University. Dr. Bernstein completed her postdoctoral studies with Dr. David Allis at The Rockefeller University. She has made important scientific contributions to various areas of biology during her career, including understanding the mechanisms underlying RNA interference and chromatin regulation, and more recently, how the latter can impact on disease. Her laboratory studies epigenetic mechanisms underlying stem cell biology and reprogramming, and cancer initiation and progression with a focus on malignant melanoma.

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Alterations in the chromatin remodeler ATRX define a high-risk NB subgroup characterized by poor prognosis and limited therapeutic options. These alterations frequently generate ATRX in-frame fusion (IFF) proteins that lack essential chromatin-binding and interaction domains, potentially conferring new, alternative functions. Alja is particularly interested in understanding how ATRX IFFs sustain the NB phenotype by identifying novel binding partners and dissecting the mechanisms through which these fusions reprogram transcriptional networks. Her ultimate goal is to uncover critical ATRX IFF interactors that drive oncogenic transcriptional programs and represent potential therapeutic targets.

Valentina began her academic career in France where she first completed her bachelor’s degree in biology at Université de La Rochelle followed by a Master’s degree in research biomedicine at Université de Strasbourg. Valentina developed an interest in melanoma research while carrying out an internship at Laboratoire de Bioimagerie et Pathologies where she investigated how the positioning of various intracellular organelles affected migration and extracellular matrix degradation linked to melanoma progression. In Dr. Bernstein’s team, she is currently involved in understanding the role of macroH2A function in melanoma pathogenesis using mouse models. Outside the lab, Valentina enjoys working out, exploring the city and cooking new dishes.

Histone variants are incorporated and exchanged at specific regions of the genome to regulate homeostasis and cellular identity. As such, histone variant dysfunction has profound consequences for tumor cells; however, the role of these chromatin components in the tumor microenvironment (TME) remains unclear. Using an autochthonous, immunocompetent primary melanoma model, Dan showed that mice devoid of the histone variant macroH2A develop larger tumors, underpinning a compromised anti-tumor immune response. This stems from intrinsic upregulation of inflammatory genes in cancer-associated fibroblasts (CAFs), where macroH2A deficiency leads to rewiring of 3D chromatin interactions. Dan is using his expertise with in vivo tumor models, in vitro cell biology, various modalities of large-scale data analysis (e.g., single cell RNA-seq, spatial transcriptomics, and epigenomics), and distinct compartments of the TME, to define how epigenetic modulation of CAFs directs their phenotype, in turn affecting immune cell activity in melanoma.

Dr. Carcamo is a senior bioinformatician in the Bioinformatics for Next Generation Sequencing (BiNGS) Shared Resource of the Mount Sinai Tisch Cancer Center. Dr. Carcamo’s thesis dissertation focused on chromatin remodeling alterations in cancer. He has expertise in performing and analyzing epigenetic and transcriptomic genome-wide datasets. More specifically, Dr. Carcamo is an expert in analyzing ATAC- and ChIP-seq data, integration of epigenetic and transcriptomic data, and the analysis of TF networks.