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Keith Choate, MD, PhD

Aaron B. and Marguerite Lerner Professor and Chair of Dermatology. Professor of Genetics and Pathology. Associate Dean for Physician-Scientist Development
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About

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Aaron B. and Marguerite Lerner Professor and Chair of Dermatology. Professor of Genetics and Pathology. Associate Dean for Physician-Scientist Development

Biography

Keith Choate M.D., Ph.D., is a physician-scientist who employs tools of human genetics to understand fundamental mechanisms of disease. His laboratory studies rare inherited and mosaic skin disorders to identify novel genes responsible for epidermal differentiation and development. His laboratory has identified the genetic basis of over 12 disorders and has developed new therapeutic approaches informed by genetic findings. His laboratory is funded by the National Institute of Arthritis and of Musculoskeletal and Skin Diseases, a division of the National Institutes of Health.

Dr. Choate mentors undergraduate, graduate, and medical students in his laboratory, teaches at Yale Medical School, and trains resident physicians and fellows.

Appointments

Education & Training

Resident
Yale- New Haven Hospital (2008)
Postdoctoral Fellow
Yale University School of Medicine (2008)
Intern
Yale-New Haven Hospital (2005)
MD
Yale University School of Medicine (2004)
PhD
Yale University, Cell Biology (2001)
MPhil
Yale University, Cell Biology (2000)
BS
Stanford University, Biological Sciences (1995)

Research

Overview

Genetics has informed our understanding of normal skin development and differentiation, largely due to the fact that mutations affecting the skin result in easily observed phenotypes. Genetic investigation has permitted us to identify a priori pathways previously unrecognized to be relevant to skin biology. These insights have been relevant to diagnosis, disease prevention, and development of novel therapeutics.

We have three ongoing projects in the lab:

1. Identification of novel genetic causes of inherited skin disorders including ichthyosis, inflammatory disorders and alopecia. We have developed one of the largest registries of kindreds with ichthyosis and have identified over 10 new genetic cause of this group of disorders – we employ cell, murine, and engineered tissue models to understand that biological basis of disease and the role of novel genes in disease pathobiology.

2. Identification of novel genetic causes of mosaic skin disorders including childhood malformations, vascular tumors, and linear presentations of inflammatory disorders. Mosaic disorders are the result of embryonic somatic mutation, with timing of mutation determining the extent of disease. Among other discoveries, we have systematically dissected pathways leading to development of aggressive infantile vascular tumors, identified novel causes of acne pathogenesis and hair follicle differentiation, and have identified Ras as a regulator of phosphate homeostasis. A new project is focused on linear manifestation of common inflammatory disorders such as lupus, psoriasis, and lichen planus with the expectation that investigation will identify novel pathways in cutaneous innate immunity.

3. Elucidation of mechanisms of revertant mosaicism in ichthyosis with confetti to enable therapeutic recombination in the skin. We have found that specific mutations in KRT1 and KRT10 cause ichthyosis with confetti which undergoes spontaneous self-correction via revertant mosaicism, resulting in hundreds to thousands of patches of normal skin. All spots arise from mitotic recombination, and have found that keratin mutations directly influence DNA damage and repair and that cellular competition favors reversion. We are employing forward genetics to identify the pathways relevant to recombination and competition.

Medical Subject Headings (MeSH)

Cell Biology; Genetics; Genetics, Medical; Human Genetics; Human Genome Project; Ichthyosis; Mosaicism; Skin and Connective Tissue Diseases; Skin Diseases

Research at a Glance

Yale Co-Authors

Frequent collaborators of Keith Choate's published research.

Publications

2024

2023

Clinical Trials

Current Trials

Academic Achievements & Community Involvement

  • activity

    Associate Director Yale Medical Scientist Training Program

  • honor

    ICC

  • activity

    Medical and Scientific Advisory Board, Foundation for Ichthyosis and Related Skin Types

  • activity

    Board of Directors, Foundation for Ichthyosis and Related Skin Types

  • honor

    ADA

Clinical Care

Overview

Keith Choate, MD, PhD, is a professor of dermatology, genetics and pathology at Yale School of Medicine and a medical dermatologist who treats patients with a variety of skin conditions, including skin cancer, severe acne, psoriasis, and other conditions upon referral by a dermatologist. His expertise in genetic skin disorders leads to referrals from across the country and around the world. Regarding the complex cases he sees, Dr. Choate says, “There's nothing better than solving a medical mystery, and it’s enormously gratifying to see patients get better.”

He reports that some patients have seen many other doctors before coming to Yale Medicine Dermatology, and that they are surprised to discover how things are done differently at Yale Medicine. As a physician-scientist, Dr. Choate and others in the department bring insights from scientific investigation and clinical trials to patient care. “At the end of the day, there's always an answer to complex skin problems if we are willing to work together toward finding a solution,” says Dr. Choate.

Dr. Choate is co-chief of dermatology at the Saint Raphael campus, director of research of the Yale Medicine Department of Dermatology, and an associate director of the Yale Medical Scientist Program. He reports that “having the opportunity to train the next generation of clinicians and physician-scientists who will shape medicine is an inspiring part of what I do.”

In his own research, Dr. Choate employs genetic tool and biologic investigation to find solutions for other genetic disorders such as ichthyosis, palmoplantar keratoderma and disorders appearing in patches or stripes on the skin. These include mosaic manifestations of acne, lichen planus, lupus and psoriasis.

To that end, Dr. Choate has recently published research on a group of severe, genetic skin conditions called ichthyosis, which cause dry, scaly or thickened skin. They affect about 200,000 people and can be disfiguring. In his new research, he and colleagues found a commonly used acne medication called isotretinoin (Accutane), counteracts the effects of the genetic mutations the disorder causes. “In two patients who’ve utilized it, the medication has cured the disease,” Dr. Choate says.

“Yale Medicine’s approach to patient care, disease-centered research, and education gives me a unique opportunity to make a difference in patients’ lives. This is why I come to work every day,” Dr. Choate says.

Clinical Specialties

Dermatology; Pediatric Dermatology

Fact Sheets

Board Certifications

  • Dermatology

    Certification Organization
    AB of Dermatology
    Original Certification Date
    2008

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