Skip to Main Content
Directory of Faculty Research Interests
YSM Home

INFORMATION FOR

DownloadHi-Res Photo

Pramod Mistry

MBBS, PhD, MA, MD
Professor of Medicine (Digestive Diseases) and of Pediatrics (Gastroenterology); Professor of Cellular & Molecular Physiology; Director of Yale Lysosomal Disease Center and Gaucher Disease Treatment Center

Contact Information

Pramod Mistry, MBBS, PhD, MA, MD

Mailing Address

  • Yale School of Medicine

    Department of Medicine (Digestive Diseases), PO Box 208019

    New Haven, CT 06520-8019

    United States

Mistry Lab
Download CV

Related Links

Yale Medicine

Patient Care

Are you a patient?Please visit the Yale Medicine website for information about the services we offer and making an appointment.View Doctor Profile

Research Summary

The major focus of my research is Gaucher disease, a prototype rare lysosomal disease with emerging relevance of sphingolipid metabolism to common diseases such as Parkinson disease, cancers (myeloma, B cell malignancies and HCC) and pulmonary arterial hypertension. The key areas that are under active investigations are:

  1. Development of clinical tools to define the spectrum, severity and sub-types of Gaucher disease;
  2. Biomarker discovery to aid patient monitoring and understand disease mechanisms;
  3. We are participating in several clinical trials of recombinant enzyme replacement therapies and small molecule therapies for Gaucher disease.
  4. We have developed numerous mouse models of Gaucher disease including humanized mouse models. This is a key development to enable mechanistic understanding of Gaucher disease and develop novel treatments. These models are advancing understanding of glycosphingolipid/myeloid cell interaction underlying systemic inflammation and neuroinflammation in GBA-associated neuronopathic syndromes and Parkinson disease. We are applying Lipidomics, scRNAseq and snRNAseq in these models and in clinical translation patient cells and humanized mouse models.
  5. We are conducting WES/WGS studies of large Gaucher disease patient populations to understand the role of modifier genes to advance precision medicine.


Specialized Terms: Gaucher disease; Mouse models, WES/WGS, disease mechanisms, therapies.

Extensive Research Description

We have focused on deep clinical phenotyping of patients as the foundation of genomic, biomarker and modifier gene studies in Gaucher disease. This approach has also allowed forumating key research questions tgo the lab and out extensive collection of mouse models. In this way, our program represents iterative bedside to bench and back to bench research program that makes incremental improvement in patient care and outcomes. We collaborate with international colleagues to decipher global patterns of disease, genotypes, phenotypes and natural history. Our in- house Registry and International Collaborative Gaucher Registry has propelled and validated numerous basic mechanistic findings derived from our lab studies using cells and mouse models. In the clinic, we are a site for clinical trials of recombinant enzyme replacement therapy and small molecule therapy. Pre-clinical studies on gene editing therapy are in progress.

Gaucher disease shows extraordinary phenotypic varaiabilty even among affected sib-pairs and among patients with identical genotypes. We are examining several candidate genes in glycosphingolipid metabolic pathways and in pro-inflammatory pathways as potential modifier genes. We are also applying several genomic approaches (WES, WGS, scRNAseq snRNAseq) for identification of modifier genes. Discovery of modifier genes will impact on patient management through more accurate prediction of prognosis and enable pre-emptive therapy of those at highest risk.

Rare Gaucher disease is also illuminating common diseases such as B cell malignancies, hepatocellular carcinoma and Parkinson disease. Patient with Gaucher disease are at high risk of these complications and interestingly even heterozygote carriers of GBA mutations are at increased risk of Parkinson disease. We are actively studying these links and researching into underlying mechanisms.

Our clinical translational model developed for Gaucher disease is applicable for a range of inborn errors of metabolism affecting the liver such as Glycogen Storage disease type 1a, porphyrias, Wilson disease, alpha 1 antitrypsin deficiency and hemochromatosis.

Coauthors

Research Interests

Digestive System Diseases; Egypt; Gastroenterology; Gaucher Disease; Genotype; Glycogen Storage Disease Type I; India; Lipid Metabolism, Inborn Errors; Multiple Myeloma; Pediatrics; Phenotype; Physiology; Lysosomal Storage Diseases; alpha 1-Antitrypsin Deficiency; Lysosomal Storage Diseases, Nervous System; Lipid Metabolism Disorders; Familial Primary Pulmonary Hypertension; Parkinson Disease Associated Proteins

Research Image

Conditional KO mouse model recapitulates type 1 Gaucher disease

Germline KO of Gaucher disease gene is lethal. We developed conditional KO model LoxP-GBA-LoxP/Mx1Cre to induce GBA gene deletion after birth in hematopoietic and mesenchymal cells.

Selected Publications

Clinical Trials

ConditionsStudy Title
Hepatitis; HIV/AIDS; Immune System; Infectious DiseasesScreening In Anticipation of Future Research
Edit Profile