Shashikant Kulkarni, M.S. (Med), Ph.D., MBA, FACMG
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Positions
- Professor
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Molecular and Human Genetics
Baylor College of Medicine
Houston, TX US
- Vice Chair of Research Affairs
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Molecular and Human Genetics
Baylor College of Medicine
- Chief Scientific Officer
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Baylor Genetics
- Senior Vice President of Innovation
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Baylor Genetics
- Co-Program Director
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American Board of Medical Genetics and Genomics (ABMGG) Laboratory Genetics Fellowship, Molecular and Human Genetics
Baylor College of Medicine
Houston, Texas
- Member
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Dan L Duncan Comprehensive Cancer Center
Baylor College of Medicine
Houston, Texas United States
Education
- Clinical Fellowship at Harvard Medical School, Brigham and Women's Hospital
- Boston, Massachusetts United States
- Research Fellowship at Hammersmith Hospital, Imperial College
- London, United Kingdom
- PhD from All India Institute of Medical Sciences
- New Delhi, India
- Medical Genetics
Certifications
- Clinical Molecular Genetics and Genomics
- #Board Certified
- American Board of Medical Genetics and Genomics
- Clinical Cytogenetics and Genomics
- #Board Certified
- American Board of Medical Genetics and Genomics
Professional Statement
Integrated multi-omic approaches to understand constitutional and acquired genomic disorders by elucidating alterations and mechanisms relevant for pathogenesis: We use whole genome, exome and transcriptome sequencing to discover recurring mutations that are potentially relevant for human genomic disorders. Some examples include Acute Myeloid Leukemia (AML) pathogenesis and clonal diversity and relapse (Cell and Nature 2012; NEJM 2013). As a proof of concept, we have successfully performed clinical whole genome sequencing on AML patients with diagnostic uncertainty in clinically relevant timeframe to find clinically actionable findings (JAMA 2012). These efforts are being extended to evaluate the clinical utility of genomic sequencing in several tumor types both in germline and somatic setting (Cell 2018; Hum Mut 2018). Current active translational research collaborations with clinical colleagues and basic researchers focuses on: 1) early detection of pancreatic cancer using proteomics, transcriptomics and genomics; 2) proteo- genomic approaches using kinase coated beads and mass spectrometry to repurpose FDA-approved drugs in breast cancer; 3) transcriptomic profiling in bladder cancer and 4) whole genome and transcriptome- based testing in pediatric cancers.Developing Standards and Guidelines for the Interpretation of Sequence Variants: One of the major bottlenecks for implementation of individualized genomic medicine is lack of clinical-grade genomic knowledgebase to facilitate consistent clinical interpretation of sequence variants. Our group is one of several participating laboratories of a major NHGRI/NIH funded multi-institutional effort called ClinGen (Clinical Genome Resource Program). The purpose of ClinGen (http://clinicalgenome.org) is to create a centralized repository and interconnected resources of clinically relevant variants, which are critically needed by the clinical and research communities. We are expanding the scope of this effort by creating somatic variant expert curation of clinically actionable knowledge (Gen Med 2017, Hum Mut 2018, Gen Med 2020, NPJ Gen Med 2020). This expert-curated variant interpretation somatic variation database which will be housed at publicly available NCBI’s ClinVar database.
Design and Optimization of Next-Generation Sequencing Technical and Informatics Pipelines for Clinical Laboratory Practice: We are actively involved in defining standards for next generation sequencing in clinical diagnostics in collaboration with the Centers for Disease Control and Prevention through the Clinical Next-Generation Sequencing Quality Standards National Working Group comprised of key opinion leaders in the field (J Mol Diag 2018, Nat Biotech 2012, Nat Biotech 2015). Additionally, we are working with Clinical Laboratory Standards Institute’s (www.CLSI.org) professional guidelines committee. CLSI standards and guidelines are considered gold standard and are followed by clinical labs nationally and internationally for raising levels of quality, safety and efficiency in laboratory testing and reporting.
Websites
Selected Publications
- Marshall CR, Bick D, Belmont JW, Taylor SL, Ashley E, Dimmock D, Jobanputra V, Kearney HM, Kulkarni S, Rehm H "The Medical Genome Initiative: moving whole-genome sequencing for rare disease diagnosis to the clinic.." Genome Med. 2020;12:48.
- Marshall CR, Chowdhury S, Taft RJ, Lebo MS, (..), Kulkarni S, Taylor SL, Belmont JW, Stavropoulos DJ, Lennon NJ "Best practices for the analytical validation of clinical whole-genome sequencing intended for the diagnosis of germline disease.." NPJ Genom Med. 2020;5:47.
- Hayeems RZ, Dimmock D, Bick D, Belmont JW, Green RC, Lanpher B, Jobanputra V, Mendoza R, Kulkarni S, Grove ME, Taylor SL, Ashley E "Clinical utility of genomic sequencing: a measurement toolkit.." NPJ Genom Med.. 2020;5:56.
- Huselton E, Rettig MP, Fletcher T, (..), Kulkarni S, Ghobadi A, Abboud C, Cashen AF, Stockerl-Goldstein K, Uy GL, Vij R, Westervelt P, DiPersio JF, Schroeder MA "A phase I trial evaluating the effects of plerixafor, G-CSF, and azacitidine for the treatment of myelodysplastic syndromes.." Leuk Lymphoma. 2021;1-14.
- Huang KL, Mashl RJ, Wu Y, Ritter DI, (...), Kulkarni S, Dipersio JF, Reimand J, Meric-Bernstam F, Chen K, Shmulevich I, Plon SE, Chen F, Ding L "Pathogenic Germline Variants in 10,389 Adult Cancers.." Cell. 2018;173:355-370.e14.
- Li MM, Datto M, Duncavage EJ, Kulkarni S, Lindeman NI, Roy S, Tsimberidou AM, Vnencak-Jones CL, Wolff DJ, Younes A, Nikiforova MN "Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer: A Joint Consensus Recommendation of the Association for Molecular Pathology, American Society of Clinical Oncology, and College of American Pathologists.." J Mol Diagn.. 2017;19:4-23.
- Griffith M, Griffith OL, Krysiak K, (...), Kulkarni S, DiPersio JF, Mardis E, Wilson RK, Ley TJ "Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia." Exp Hematol. 2016 Jul;44:603-613. Pubmed PMID: 27181063
- Griffith M, Miller C, Griffith O, (...), Kulkarni S, Cordes M, Fronick C, Fulton R, Maher C, Ding L, Klco J, Mardis E, Ley T, Wilson R "Optimizing Cancer Genome Sequencing and Analysis." Cell Systems. 2015 Sep 23;1:210-323. Pubmed PMID: 26645048
- Klco J, Miller C, Griffith M, (...), Kulkarni S, Ozenberger B, Welch J, Walter M, Graubert T, Westervelt, P, Radich J, Link D, Mardis E, DiPersio, J, Wilson R, Ley T. "Association Between Mutation Clearance After Induction Therapy and Outcomes in Acute Myeloid Leukemia." JAMA. 2015 Aug 15;314:811-22. Pubmed PMID: 26305651
- Gargis AS, Kalman L, Bick DP, Da Silva C, Dimmock DP, Funke BH, Gowrisankar S, Hedge MR, Kulkarni S, et. al "Good laboratory practive for clinical next-generation sequencing informatics pipelines." Nat Biotechnol. 2015 Jul;33:689-93. Pubmed PMID: 26154004
- Ungewickell A, Bhanduri A, Rios E, Reuter J, Lee C, Mah A, Zehnder A, Ohgami R, Kulkarni S, Armstorng R, Weng W, Gratzinger D, Tavallaee M, Rook A, Snyder M, Kim Y, Khavari P "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2." Nat Genet. 2015 Sep;47:1056-60. Pubmed PMID: 26258847
- Lyon E, Cockerill FR 3rd, Bale SJ, Beadling C, Bry L, Hagenkord J, Kulkarni S, Press R, Palomaki GE "Next generation sequencing in clinical diagnostics: experiences of early adopters." Clin Chem. 2015 Jan;61:41-9. Pubmed PMID: 25421800
- Perrino CM, Hucthagowder V, Evenson M, Kulkarni S, Humphrey PA "Genetic alterations in renal cell carcinoma with rhabdoid differentiation." Hum Pathol. 2015 Jan;46:9-16. Pubmed PMID: 25439741
- Hagemann IS, Devarakonda S, Lockwood CM, Spencer DH, Guebert K, Bredemeyer AJ, Al-Kateb H, Nguyen TT, Duncavage EJ, Cottrell CE, Kulkarni S, et. al. "Clinical next-generation sequencing in patients with non-small cell lung cancer." Cancer. 2015 Feb 15;121:631-9. Pubmed PMID: 25345567
- Welch JS, Ley TJ, Link DC, (...), Kulkarni S, Klco JM, Tomasson MH, Westervelt P, Walter MJ, Graubert TA, DiPersio JF, Ding L, Mardis ER, Wilson RK "The origin and evolution of mutations in acute myeloid leukemia." Cell. 2012 Jul 20;150:264-78. Pubmed PMID: 22817890
- Ding L, Ley TJ, Larson DE, (...), Kulkarni S, Westervelt P, Walter MJ, Graubert TA, Mardis ER, Wilson RK, DiPersio JF "Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing." Nature. 2012 Jan 11;481:506-10. Pubmed PMID: 22237025
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