Genetic & Genomic Research | Icahn School of Medicine

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Department of Genetics and Genomic Sciences

Research at the Department of Genetics and Genomic Sciences spans multiple interconnected areas—from cancer genomics and neurogenomics to immunogenomics, microbial genomics, and drug development—united by a shared commitment to understanding how genetic variation drives human disease. Our faculty bring together basic and translational researchers, computational biologists, data scientists, and technology innovators who leverage large-scale multi-omic data, advanced sequencing platforms, and cutting-edge computational tools to accelerate discovery across a broad spectrum of conditions.

By bringing together discovery science, advanced technologies, clinical expertise, and clinical research within a single department, we accelerate the translation of genomic insights into new diagnostics, therapies, and clinical trials. From preclinical innovation to first-in-human trials and FDA-approved therapies, our work is designed to translate—bringing genetically informed treatments to patients with rare diseases, neurological conditions, cancer, metabolic disorders, and beyond.

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Research Areas

Cancer is a disease driven by genetic changes that disrupt normal cellular processes—including growth, proliferation, and survival—and can lead to tumors or blood diseases such as leukemia. Our researchers investigate the mechanisms by which cells acquire the capacity for cancerous transformation, working across disciplines to uncover the molecular underpinnings of malignancy and develop new strategies for cancer prevention, diagnosis, and treatment.

To advance precision oncology, our team integrates a broad range of technologies, including genomic analysis of inherited and acquired mutations, RNA expression profiling, proteomics, epigenetic mapping, imaging, and single-cell and spatial sequencing. These approaches are used to predict cancer risk, identify tumor vulnerabilities, and inform personalized therapeutic strategies. Our researchers are also pioneering new methods for sample isolation, molecular profiling, and multi-modal data integration—work that has led to key insights into how cancers rewire signaling pathways to initiate disease, sustain uncontrolled growth, and evade the immune system.

Cancer genetics researchers include:

At the intersection of neuroscience, genetics, and genomics, researchers in the Department of Genetics and Genomic Sciences are uncovering the molecular mechanisms that drive neurological and psychiatric conditions. Using multi-omic technologies and innovative computational tools, our team is advancing therapeutic discovery across a wide range of neurodevelopmental, neuropsychiatric, and neurodegenerative disorders—developing novel statistical models, biological network methods, and experimental systems for disease modeling in close collaboration with leading institutional partners across the Mount Sinai Health System.

Our Alzheimer's disease research builds on genome-wide association studies that have identified germline variants enriched in myeloid-specific enhancers, highlighting the role of microglia—the brain's resident immune cells—in disease etiology. These variants influence risk through epigenetic regulation of genes involved in microglial function, and by investigating the clearance of dead cells, our team aims to identify and prioritize therapeutic targets for modifying disease progression. In parallel, our researchers investigate the role of somatic mutations—both sequence and copy number changes that arise after fertilization and accumulate with age—in healthy and diseased brain tissue, shedding light on how genetic mosaicism contributes to neurodevelopmental and neurodegenerative disease, including autism spectrum disorders. Across all of these efforts, our team leads in the integration of machine learning and artificial intelligence approaches to map disease-relevant biological networks, combining single-cell and cell-type-specific multi-omic data with functional studies to identify critical network drivers and accelerate the discovery of therapeutic targets for complex brain disorders.

Neurogenomics researchers include:

Rare diseases are individually uncommon but collectively affect millions of people, many of whom face years of uncertainty before receiving an accurate diagnosis. The Department of Genetics and Genomic Sciences brings together basic scientists, computational researchers, physician-scientists, and clinicians to identify the genetic causes of rare and undiagnosed conditions, determine how disease-associated variants alter biological function, and translate these discoveries into better diagnosis, disease management, and treatment. Our research spans neurodevelopmental, metabolic, lysosomal, immune, craniofacial, cardiovascular, and other multisystem disorders affecting children and adults.

Our researchers use whole-genome and whole-exome sequencing, statistical and population genomics, functional genomics, multi-omic analysis, biochemical studies, and patient-derived and animal models to discover disease-causing genes and variants and uncover their biological consequences. This work is closely integrated with the Department’s Division of Medical Genetics and Genomics, a National Organization for Rare Disorders (NORD) Rare Disease Center of Excellence that provides specialized care to children and adults with rare genetic conditions. Through the Division and collaborative initiatives, including the Mount Sinai Center for Undiagnosed Diseases and INDEED Study, investigators connect advanced genomic analysis with clinical phenotyping, natural-history studies, and mechanistic research. This research continuum helps provide answers to patients and families, establish newly recognized genetic disorders, inform clinical guidelines, and lay the foundation for therapeutic development—from foundational preclinical research through first-in-human studies and approved therapies.

Rare Disease researchers include:

The immune system plays a central role in human health—fighting infections, eliminating cancer cells, and maintaining internal balance. When immune responses go awry, they can drive inflammation, autoimmunity, and chronic disease. Our laboratory, computational, and clinical scientists work together to identify the genetic variants that drive immune cell responses, both protective and pathogenic. This includes studying the dynamic interplay between tumor cells and the immune system to reveal how tumor-associated genetic drivers influence immune biology and response to immunotherapy, as well as investigating how genetics, the immune system, and environmental factors interact in inflammatory bowel disease.

Foundational discoveries in this area—including the identification of mutations associated with Crohn's disease and genetic variants in interleukin-23 receptor signaling linked to both Crohn's disease and ulcerative colitis—contributed directly to the development of anti-interleukin-23 immunotherapies now widely used in treatment. Our researchers are also uncovering critical neuro-immune interactions, identifying Alzheimer's disease risk genotypes associated with altered function in microglia—the brain's resident immune cells—and revealing key genetic drivers and regulatory networks that shape neuro-immune dynamics in autism spectrum disorders.

Immunogenomics researchers include:

Microbial genomics is transforming our understanding of infectious disease, immunity, and human health. Researchers in the Department of Genetics and Genomic Sciences use cutting-edge genomic tools to track pathogens, study host-microbe interactions, and develop microbial-based therapies. Our Pathogen Surveillance Program brings together experts in infectious disease, genomics, epidemiology, and computational modeling to monitor and characterize viral and bacterial threats—including the virus responsible for the COVID-19 pandemic. Using advanced whole-genome sequencing and bioinformatics, our researchers study the evolution, transmission, and host interactions of infectious agents, including identifying emerging pathogens and genetic variants with the potential to drive outbreaks.

Beyond pathogens, our scientists use both experimental and computational approaches to study how microbial communities influence inflammatory bowel disease, allergies, COVID-19, influenza, cancer, and other conditions—work that has led to innovative treatment strategies including microbiota transplants, with two active clinical trials investigating microbial therapies for inflammatory bowel disease and food allergies. Additional research is focused on antibiotic resistance, opportunistic infections, and the complex communities of bacteria, fungi, and viruses that coexist within the human body, with specialized tools being developed to analyze challenging tissue types and advance the design of next-generation microbial therapeutics.

Microbial genomics and pathogen surveillance researchers include:

The increasing scale and complexity of high-dimensional data—generated by advanced sequencing, molecular profiling, and clinical systems—requires powerful analytical approaches to extract meaningful insights. At the Icahn School of Medicine at Mount Sinai, computational biology is central to modern genetics and genomics research. Our team includes experts in biostatistics, machine learning, data science, and software engineering, all working to develop innovative solutions for large-scale genomic analysis and uncover the molecular underpinnings of disease.

Key areas of focus include algorithm development for disease risk prediction using genetic and clinical data, functional annotation of genetic variants and genes, and integrative multi-omic analysis for improving diagnosis, prognosis, and treatment response prediction. We are also applying drug discovery informatics—including computational tools to predict drug response, toxicity, and identify novel therapeutic targets—and model gene and protein regulatory networks to understand cellular behavior in development and disease.

A growing area of focus is clinical data science that integrates electronic health records with genetic, genomic, and multi-omic data. Our investigators use machine learning and natural language processing to analyze structured clinical information and clinical notes, identify individuals with undiagnosed or rare genetic disorders, define pre-diagnostic phenotypes, study variable disease expression, and reduce diagnostic delay. These approaches also support patient finding and research cohort development, risk prediction and stratification, and the validation of biomarkers and computational drug-discovery findings using large-scale clinical data—helping translate genomic insights into earlier diagnosis and more precise care.

Computational biology, bioinformatics, and artificial intelligence researchers include:

Functional genomics integrates genome-wide technologies, computational modeling, and laboratory validation to systematically investigate the molecular mechanisms driving human disease. Our team brings together experimental and computational expertise to apply functional genomics across a wide range of conditions, advancing both discovery science and clinical translation.

Recent achievements include the development of a spatial functional genomics platform that enables parallel knockout of dozens of genes in a mouse model of lung cancer, with simultaneous assessment of effects on tumor growth, histopathology, and immune cell composition. Our team advanced and applied bulk, single-cell, and spatial multi-omic techniques—coupled with robust data integration methods—to generate and interpret large-scale, multidimensional datasets that drive discovery and inform clinical translation. Additional work includes the development of computational frameworks to map gene regulatory networks and uncover the functional roles of disease-associated genes and variants at the cellular level, as well as the use of multimodal neuroimaging and genomic data to enhance the diagnosis of psychiatric disorders and support the development of targeted therapeutics.

Functional genomics researchers include:

Breakthroughs in gene editing technologies—including CRISPR/Cas9 and transcription activator-like effector nucleases—have made it possible to precisely modify the genome, enabling the creation of highly accurate cellular and animal models of disease and opening transformative possibilities for treating genetic disorders through targeted gene and cell therapies. We are advancing these precision techniques to modify gene and cell function, driving progress in both fundamental biology and translational research.

Beyond gene editing, our researchers use modified RNA and a variety of viral and non-viral vectors to introduce genes or proteins into cells, reprogramming cellular behavior for therapeutic or experimental purposes. These technologies are applied to both somatic and stem cells, including induced pluripotent stem cells—which can be differentiated into multiple tissue types—allowing researchers to model normal development, study disease progression, investigate tissue regeneration, and conduct drug screening in systems that closely mimic human biology. When combined with gene editing, induced pluripotent stem cells can be used to generate patient-specific disease models, explore therapeutic responses, and correct genetic defects, laying the foundation for personalized regenerative medicine. This work spans cardiovascular, neurodegenerative, hematologic, immune, metabolic, hereditary, and oncologic diseases.

Gene editing and cell engineering researchers include:

The defining strength of the Department of Genetics and Genomic Sciences is a strong focus on the development and integration of cutting-edge genomic technologies. These tools are seamlessly embedded across the research programs of our faculty and play a central role in advancing both discovery science and clinical translation. Ongoing advances in genome editing, sequencing, and functional characterization have transformed our understanding of the genome, epigenome, and transcriptome, accelerating progress across precision medicine, oncology, immunology, neuroscience, and infectious disease.

Our researchers lead the development and application of multi-omic methods across model systems and patient cohorts to address complex biological questions. By integrating bulk and long-read sequencing, single-cell analysis, open chromatin profiling, and spatial transcriptomics, our team has generated insights into the molecular basis of drug addiction, cancer immunotherapy response, Alzheimer's disease, and COVID-19.

The Department is supported by a robust infrastructure of genomic technologies—including ultra-low-input library preparation for limited or degraded samples, targeted gene profiling for DNA and RNA applications, amplification-free enrichment strategies, and short-read and long-read sequencing platforms spanning single-molecule and nanopore techniques applied across bulk samples, single cells, and intact tissues. This infrastructure is coupled with deep domain expertise in experimental design, innovative technology applications, and bioinformatic analysis, enabling our team to push the boundaries of genomic science and generate new data and methodologies that shape the future of research at Mount Sinai and through global collaborations.

Technology development researchers include:

The Department of Genetics and Genomic Sciences and the Icahn Genomics Institute are committed to translating genomic discoveries into therapies that improve patients' lives. Our faculty lead drug development efforts spanning from preclinical innovation to pivotal clinical trials, with a strong focus on rare genetic diseases, neurodegeneration, metabolic disorders, and precision therapeutics. We have a track record of advancing therapies through close integration of cutting-edge molecular research, advanced analytics, and clinical expertise.

Our researchers have contributed to the development and clinical evaluation of multiple FDA-approved therapies, including Fabrazyme (agalsidase beta) for Fabry disease, Xenpozyme (olipudase alfa-rpcp) for acid sphingomyelinase deficiency (ASMD), historically known as Niemann-Pick disease, and Givlaari (givosiran), an RNA interference therapy for acute hepatic porphyria (link to: https://www.mountsinai.org/care/genetics/services/porphyria-diagnostic-treatment).

Selected preclinical studies include research evaluating in vivo gene editing for Fabry disease, RNA interference for acute intermittent porphyria, and enzyme replacement for acid sphingomyelinase deficiency. Additional areas of investigation include adeno-associated virus-mediated gene delivery, pharmacological chaperone therapies for genetic diseases, and diagnostic tools and therapeutic approaches for congenital disorders of glycosylation.

Drug development and clinical trial researchers include: