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Picture of Dr. Shyam Sharan

Shyam K. Sharan, Ph.D.

  • Center for Cancer Research
  • National Cancer Institute
Senior Investigator
Head, Genetics of Cancer Susceptibility Section
Director, Center for Advanced Preclinical Research

RESEARCH SUMMARY

Breast cancer is one of most common malignancies in women. Mutations in BRCA1 and BRCA2 are linked to increased risk of early onset familial breast and ovarian cancers. In an effort to reduce the mortality due to breast cancer through prevention and early diagnosis, sequencing based genetic tests are available to identify BRCA1 and BRCA2 mutation carriers. Such tests have led to identification of several hundreds of sequence variants that are of unknown clinical significance. We are using mouse embryonic stem cells as well as humanized and knock-in mouse models to distinguish between neutral or non-pathogenic and deleterious or pathogenic variants. Dr. Sharan is Deputy Director of the Mouse Cancer Genetics Program (MCGP). Dr. Sharan is also Director of the Center for Advanced Preclinical Research (CAPR) and heads the BRCA Variants Analysis Unit. A list of classified variants can be found on this link to the BRCA Variants Analysis Unit.

Areas of Expertise

DNA Repair
Tumor Suppressor
Mouse Models

Publications

Selected Key Publications

Spatiotemporal modulation of growth factors directs the generation of multilineage mouse embryonic stem cell-derived mammary organoids.

Sahu S, Sahoo S, Sullivan T, O'Sullivan TN, Turan S, Albaugh ME, Burkett S, Tran B, Salomon DS, Kozlov SV, Koehler KR, Jolly MK, Sharan SK.
Dev Cell. 759(2): 175-186, 2024.
Full-Text Article
[ Journal Article ]

Mismatch repair protein MLH1 suppresses replicative stress in BRCA2-deficient breast tumors.

Sengodan SK, Hu X, Peddibhotla V, Balamurugan K, Mitrophanov AY, McKennett L, Kharat SS, Sanawar R, Singh VK, Albaugh ME, Burkett SS, Zhao Y, Tran B, Malys T, Sterneck E, De S, Sharan SK.
J Clin Invest.. 134(7): e173718, 2024.
Full-Text Article
[ Journal Article ]

Degradation of 5hmC-marked stalled replication forks by APE1 causes genomic instability.

Kharat SS, Ding X, Swaminathan D, Suresh A, Singh M, Sengodan SK, Burkett S, Marks H, Pamala C, He Y, Fox SD, Buehler EC, Muegge K, Martin SE, Sharan SK.
Sci Signal. 18;13(645):eaba8091. doi: 10.1126/scisignal.aba8091: 2020. [ Journal Article ]

Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155

Chang S, Wang RH, Akagi K, Kim KA, Martin BK, Cavallone L; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), Haines DC, Basik M, Mai P, Poggi E, Isaacs C, Looi LM, Mun KS, Greene MH, Byers SW, Teo SH, Deng CX, Sharan SK
Nat Med. 17(10):1275-82. doi: 10.1038/nm.2459: 2011. [ Journal Article ]

Mouse embryonic stem cell-based functional assay to evaluate mutations in BRCA2

Kuznetsov SG, Liu P, Sharan SK
Nat Med. 14(8):875-81. doi: 10.1038/nm.1719: 2008. [ Journal Article ]

Job Vacancies

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Team

Research Associate I (Contr.)
Mary Albaugh
Postdoctoral Fellow (Visiting)
Arun Prakash Mishra, Ph.D.
Postdoctoral Fellow (Visiting)
Sounak Sahu, Ph.D.
Postdoctoral Fellow (Visiting)
Satheesh Sengodan, Ph.D.
Biological Laboratory Technician
Teresa Sullivan
Biological Laboratory Technician
Dylan Caylor
Postdoctoral Fellow
Swati Priya, Ph.D.
Postbac
Dillon Dierman