Martha A. Zeiger, M.D.
Martha A. Zeiger, M.D. is an internationally renowned endocrine surgeon and scientist who has been a leader in developing molecular diagnostics for thyroid cancer. Her research focuses on TERT gene expression regulation, molecular marker diagnostic panel development and molecular biological aspects of thyroid cancer development. She also leads a team studying and designing future pathways for the professional development of surgeon-scientists.
1) regulation of TERT gene expression
2) molecular marker panels for diagnosis and prognosis of thyroid cancer
3) professional development of future surgeon-scientists
4) adrenal tumors
5) medullary thyroid cancer
1. TERT Regulation
Telomerase activity is reactivated in the majority of malignancies, including thyroid cancer. Reactivation is achieved through transcriptional upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT), by a variety of mechanisms: promoter methylation, promoter mutations, alternative splicing, and transcription factor (TF) binding. Our laboratory investigates TERT promoter methylation status, its relationship to TF binding, and telomerase activity in TERT-mutation positive thyroid cancer cell lines.
Goal 1: Determine the allele-specific methylation status of the TERT promoter in differentiated thyroid cancer (DTC) cell lines (TPC-1 & BCPAP) heterozygous for the TERT promoter mutation by a novel nanopore Cas9-targeted sequencing method. This targeted sequencing detects methylation without bisulfite conversion, thereby distinguishing between the TERT mutant and wildtype alleles (C>T). Chromatin immunoprecipitation followed by Sanger sequencing (ChIP-seq) for transcriptional activators MYC and GABPA to determine allele-specific binding. TERT expression and telomerase activity by qPCR and qPCR-Based Telomeric Repeat Amplification Protocol (qTRAP), respectively.
Goal 2: Interrogate the causative effect of the TERT promoter mutation on methylation and factor binding by CRISPR/Cas9 editing.
2. Professional Development of Future Surgeon-Scientists
In an era of diminishing NIH funding and decreased medical reimbursements, the challenge of conducting meaningful surgical research are significant and myriad; these include constraints on academic protected time, scarce financial and educational resources.
Goal 1: Examine these challenges, study existing successful models for the development of clinician scientists and, explore the programmatic development of the future surgeon scientist. Stakeholders in this arena include: Our surgical patients, The American College of Surgeons, The American Board of Surgery, Leaders in American Surgery with a focus on funded Surgeon Scientists, Residency and Fellowship Program Directors, Surgical Trainees.
As Surgeons within the Surgical Oncology Program at NCI, NIH we are in a unique position to explore and develop the next generation of surgeon scientists. This will include examination of the current development of a tenure-track Principal Investigator at NIH and academic surgeon scientist at academic medical institutions with special focus on the challenges faced by surgeons and, the formal implementation of a surgery-focused program aimed at developing a successful career in scientific methods and inquiry. The surgical oncology programs would serve as one of several templates for surgical research programs in the country.
Goal 2: Develop the next generation of surgeon scientists
Goal 3: Advance our knowledge of surgical diseases through scientific inquiry
Goal 4: Transform the care of all surgical oncology patients through research
Selected Key Publications
Characterization of Human Telomerase Reverse Transcriptase Promoter Methylation and Transcription Factor Binding in Differentiated Thyroid Cancer Cell Lines.Genes Chromosomes & Cancer. 58(8): 530-540, 2019. [ Journal Article ]
- Cell. 159(3): 676-690, 2014. [ Journal Article ]
- New England Journal of Medicine. 367(8): 705-715, 2012. [ Journal Article ]
Association of BRAF V600E Mutation and MicroRNA Expression with Central Lymph Node Metastases in Papillary Thyroid Cancer: A Prospective Study from Four Endocrine Surgery Centers.Thyroid. 26(4): 532-542, 2016. [ Journal Article ]
RAS Mutations, and RET/PTC and PAX8/PPAR-gamma Chromosomal Rearrangements Are Also Prevalent in Benign Thyroid Lesions? Implications Thereof and A Systematic Review.Thyroid. 27(1): 39-48, 2017. [ Journal Article ]
Dr. Martha Zeiger is an internationally renowned leader in endocrine surgery, an expert in the molecular aspects of thyroid cancer and an experienced academic leader. Her primary research focus includes regulation of telomerase gene expression and, molecular markers associated with thyroid cancer diagnosis and prognosis. She received her undergraduate degree from Brown University and her medical degree from the University of Vermont College of Medicine. After serving in the United States Navy she completed her general surgical residency at Maine Medical Center in Portland, Maine. Thereafter she worked as a commander and attending surgeon at the National Naval Medical Center in Bethesda, Maryland. Dr. Zeiger then completed a Surgical Oncology Fellowship, focusing on endocrine surgery at the National Cancer Institute (NCI) in Bethesda, Maryland prior to joining the faculty at Johns Hopkins University School of Medicine. There, she built a busy endocrine surgery practice, established an endocrine surgery fellowship program, and directed an NIH-funded molecular biology laboratory for over 20 years.
While at John Hopkins, Dr. Zeiger took the lead as: Associate Dean for Postdoctoral Affairs; Professor of Surgery, Oncology, Cellular and Molecular Medicine; Associate Vice Chair of Surgery Faculty Development; and Medical Director of Business Development Strategic Alliance and Venture Technology. As Associate Dean for Postdoctoral Affairs, she oversaw 1200 research fellows in the School of Medicine. Dr. Zeiger has held numerous leadership positions in national medical societies: the American Association of Endocrine Surgeons, the American Association of Clinical Endocrinology, and the American Thyroid Association. She founded Endocrine Surgery University, an annual course for all endocrine surgery fellows in North America. She has served as American Association of Endocrine Surgeons President and is currently President-elect of The American Thyroid Association. She recently held the position of S. Hurt Watts Professor and Chair of Surgery at the University of Virginia School of Medicine prior to joining The Surgical Oncology Program at NCI, NIH.
|Andrew M. Blakely, M.D.||Assistant Research Physician|
|Jeremy L. Davis, M.D.||Assistant Research Physician|
|Elizabeth Dillard Martin||Patient Care Coordinator (Contr.)|
|Dhaval T. Patel, M.D.||Special Volunteer|
|Amynah Pradhan CRNP-F, MSN, RN||Nurse Practitioner (Contr.)|
|Shyni Simon CRNP-BC||Nurse Practitioner|
|Danielle Stewart||Program Assistant (Contr.)|