Ryan Dhindsa, MD, PhD

Dr. Ryan Dhindsa is an Assistant Professor of Pathology & Immunology at Baylor College of Medicine. His primary goal is to understand the genetic basis of human disease to uncover better therapeutics.

Education

Organizations

* Texas Children’s Hospital physicians’ licenses and credentials are reviewed prior to practicing at any of our facilities. Sections titled From the Doctor, Professional Organizations and Publications were provided by the physician’s office and were not verified by Texas Children’s Hospital.

Research interests

The Dhindsa Lab (https://www.dhindsalab.com) is dedicated to advancing precision medicine by integrating human genomics and other omics, stem cell models and computational biology. Our research focuses on three primary areas:

(1) Population-level omics. We perform very large genetic sequencing studies to understand the genetic contribution to various human diseases. We have uncovered new genetic associations and therapeutic targets for several diseases including epilepsy, diabetes, idiopathic pulmonary fibrosis and others. We also integrate other -omic modalities into our genomics studies including transcriptomics, metabolomics and proteomics to gain insight into the pathophysiology of disease-associated variants.

(2) Human stem cell models CRISPR-based functional genomics platform in human iPSC-derived neurons to identify convergent mechanisms in intellectual disability, autism spectrum disorder and epilepsy. We employ a variety of functional approaches, including single-cell RNA-sequencing, chromatin profiling, and electrophysiology assays.

(3) Computational biology & machine learning. We use population genetics and machine learning to improve the clinical interpretation of genetic variation and accelerate genetic discoveries. We are particularly interested in using machine learning and artificial intelligence to identify regions of the human genome most likely to be associated with disease when mutated.

Wang, Q.*, Dhindsa, R.S.*, Carss, K.*, Harper, A.R., Nag, A., Tachmazidou, I., Vitsios, D., Deevi, S.V.V., Mackay, A., Muthas, D., Huhn, M., Monkley, S., Olsson, H., Wasilewski, S., Smith, K.R., March, R., Platt, A., Haefliger, C., Petrovski, S. Rare variant contribution to human disease in 281,104 UK Biobank exomes. Nature. (2021). *Co-first author

Dhindsa, R.S., Mattsson, J., Nag, A., Wang, Q., Wain, L.V., Allen, R., Wigmore, E.M., Ibanez, K., Vitsios, D., Deevi, S.V., et al. Identification of a missense variant in SPDL1 associated with idiopathic pulmonary fibrosis. Communications Biology 4 (1), 1-8. (2021).

Dhindsa, R.S., Zoghbi, A.W., Krizay, D.K., Vasavda, C., Goldstein, D.B. A transcriptome-based drug discovery paradigm for neurodevelopmental disorders. Annals of Neurology, 89 (2), 199-211. (2020).

Dhindsa, R.S., Bradrick, S.S., Yao, X., Heinzen, E.L., Petrovski, S., Krueger, B.J., Johnson, M.R., Frankel, W.N., Petrou, S., Boumil, R.M., et al. Epileptic encephalopathy-causing mutations in DNM1 impair synaptic vesicle endocytosis. Neurol Genet 1, e4. (2015).

Nag, A.*, Dhindsa, R.S.*, Harper, A.R., Vitsios, D., Ahnmark, A., Bilican, B., Madeyski-Bengtson K., Zarrouki, B., Wang, Q., Smith, K., Smith, D., Challis, B., Paul, D.S., Bohlooly-Y, M., Snowden M., Baker, D., Fristch-Danielson, R., Pangalos, M.N., Petrovski, S. Human genetic evidence supports MAP3K15 inhibition as a therapeutic strategy for diabetes. Science Advances. (2022). *Co-first author

Dhindsa, R.S., Copeland, B.R., Mustoe, A.M., and Goldstein, D.B. Natural Selection Shapes Codon Usage in the Human Genome. Am J Hum Genet 107 (1), 83-95. (2020).

Vitsios, D.*, Dhindsa, R.S.*, Mitchell, J., Matelska, D., Zou, Z., Armenia, J., Wang, Q., Sidders, B., Harper, A.R., Petrovski, S. Cancer-driving mutations are enriched in genic regions intolerant to germline variation. Science Advances. (2022). *Co-first author

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