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David Sidransky, M.D.

Photo of Dr. David Sidransky, M.D.

Director, Head and Neck Cancer Research

Professor of Otolaryngology - Head and Neck Surgery

Male

Expertise: Head and Neck Cancers

Research Interests: Lung and Bladder Cancer; Head and Neck Cancer; Molecular Cancer Detection and Staging

Background

David Sidransky, M.D. is a leading expert and pioneer in the molecular genetic detection of cancer.  He is The Director of Head and Neck Cancer Research in the Department of Otolaryngology- Head and Neck Surgery at Johns Hopkins University.  David Sidransky M.D. is best known for in research in biomarkers for early detection and therapy. Currently, his research is concentrating on identifying new genetic and epigenetic changes on smoking-associated tumors, including lung cancer, head and neck cancer and bladder cancer.  His laboratory group is also investigating the molecular epidemiology of smoking induced cancers and the link between tobacco smoke and mutations of critical oncogenes (genes that when altered, can cause cancer). His group develops new human models called tumor grafts that help accelerate drug development and help isolate predictive markers for personalized cancer therapy.

Sidransky received his medical degree from Baylor College of Medicine in 1984, where he also completed a residency in internal medicine. He came to Johns Hopkins in 1988, where he completed a clinical and research fellowship in oncology.  Sidransky joined the Hopkins faculty in 1992.He has over 500 peer-reviewed publications, and has contributed more than 65 cancer reviews and chapters and also has numerous issued biotechnology patents based on detection of genetic biomarkers for cancer in many bodily fluids.  These tests are being studied in bladder, lung, and head and neck cancers, to detect malignant cells in a very early stage, before they can be identified by conventional pathology and cytology methods. These same biomarkers have been instrumental in differentiating normal tissue from malignant tissue in head and neck cancer surgery.

He has been the recipient of many other awards and honors, including the 1997 Sarstedt International prize from the German society of clinical Chemistry, the 1998 Alton Ochsner Award Relating Smoking and Health by the American College of Chest Physicians and the Richard and Hinda Rosenthal Foundation Award of the American Association of Cancer Research (AACR) for this work.  

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Titles

  • Director, Head and Neck Cancer Research
  • Professor of Otolaryngology - Head and Neck Surgery
  • Professor of Oncology
  • Professor of Pathology
  • Professor of Urology

Education

Degrees

  • B.S., Brandeis University (Massachusetts) (1981)
  • M.D., Baylor College of Medicine - Houston (Texas) (1984)

Additional Training

  • American Board of Internal Medicine (1988)
  • American Board of Medical Oncology (1991)
  • American Society for Head and Neck Surgery (1998)

Research & Publications

Research Summary

In this laboratory, we elucidate the molecular genetic changes that drive the progression of various types of cancer. We concentrate on identifying new genetic changes in smoking-associated tumors including lung cancer, head and neck cancer, and bladder cancer. We also investigate the molecular epidemiology of smoking-induced cancers and the link between tobacco smoke and mutations of critical oncogenes. Two recent discoveries are now driving our basic research—p63, a p53 family member, is commonly amplified in SCC and drives cancer progression. We know that WT p53 binds to p63 and degrades p63. Moreover, p63 binds to B56/PP2A, resulting in upregulation of b-catenin and downstream signaling. We also recently discovered BRAF mutations in 70 percent of thyroid tumors. We are identifying downstream signaling mechanisms for BRAF and are working with new BRAF inhibitors for targeted molecular therapy.

Our laboratory is best known for our efforts in molecular-detection approaches based on the identification of clonal genetic changes in many bodily fluids, including urine, saliva, stool and blood. Several major recent innovations in this area have been pioneered by our laboratory. Many of these approaches, such as the hypermethylation of p16 in human cancers and the discovery of mitochondrial mutations at high frequency in many tumor types have shed new light in the field of cancer biology and detection. We also discovered that circulating free DNA was in fact derived from tumor cells by showing that this DNA shared the identical genetic changes present in the primary tumor. This approach may one day lead to a simple blood test to detect cancers at an early stage. Our team also has led new approaches in molecular staging based on the identification of micrometastatic disease in various tumors. This approach may one day be the standard for staging patients with cancer and will allow for more aggressive therapy in patients with minimal residual disease. No matter what area we research, we always try to bridge basic research into the clinical setting.

Selected Publications

View all on Pubmed

  1. Roh, J.L.; Kang, S.K.; Minn, I.; Califano, J.A.; Sidransky, D.; Koch, W.M. p53-Reactivating small molecules induce apoptosis and enhance chemotherapeutic cytotoxicity in head and neck squamous cell carcinoma. Oral Oncol. 2010 Dec 15.
  2. Pattani, K.M.; Zhang, Z.; Demokan, S.; Glazer, C.; Loyo, M.; Goodman, S.; Sidransky, D.; Bermudez, F.; Jean-Charles, G.; McCaffrey, T.; Padhya, T.; Phelan, J.; Spivakovsky, S.; Bowne, H.Y.; Goldberg, J.D.; Rolnitzky, L.; Robbins, M.; Kerr, A.R.; Sirois, D.; Califano, J.A. Endothelin receptor type B gene promoter hypermethylation in salivary rinses is independently associated with risk of oral cavity cancer and premalignancy. Cancer Prev Res (Phila). 2010 Sep;3(9):1093-1103.
  3. Loyo, M.; Guerrero-Preston, R.; Brait, M.; Hoque, M.O.; Chuang, A.; Kim, M.S.; Sharma, R.; Liegeois, N.J.; Koch, W.M.; Califano, J.A.; Westra, W.H.; Sidransky, D. Quantitative detection of Merkel cell virus in human tissues and possible mode of transmission. Int J Cancer. 2010 Jun 15;126(12):2991-2996.
  4. Loyo, M.; Brait, M.; Kim, M.S.; Ostrow, K.L.; Jie, C.C.; Chuang, A.Y.; Califano, J.A.; Liegeois, N.J.; Begum, S.; Westra, W.H.; Hoque, M.O.; Tao, Q.; Sidransky, D. A survey of methylated candidate tumor suppressor genes in nasopharyngeal carcinoma. Int J Cancer. 2010 May 6.
  5. Lee, J.; Jang, S.J.; Benoit, N.; Hoque, M.O.; Califano, J.A.; Trink, B.; Sidransky, D.; Mao, L.; Moon, C. Presence of 5-methylcytosine in CpNpG trinucleotides in the human genome. Genomics. 2010 Aug;96(2):67-72.
  6. Huang, Y.; Chang, X.; Lee, J.; Cho, Y.G.; Zhong, X.; Park, I.S.; Liu, J.W.; Califano, J.A.; Ratovitski, E.A.; Sidransky, D.; Kim, M.S. Cigarette smoke induced promoter methylation of single-strand DNA-binding protein 2 in human esophageal squamous cell carcinoma. Int J Cancer. 2010 Jul 23.
  7. Hoque, M.O.; Brait, M.; Rosenbaum, E.; Poeta, M.L.; Pal, P.; Begum, S.; Dasgupta, S.; Carvalho, A.L.; Ahrendt, S.A.; Westra, W.H.; Sidransky, D. Genetic and epigenetic analysis of erbB signaling pathway genes in lung cancer. J Thorac Oncol. 2010 Dec;5(12):1887-1893.
  8. Durr, M.L.; Mydlarz, W.K.; Shao, C.; Zahurak, M.L.; Chuang, A.Y.; Hoque, M.O.; Westra, W.H.; Liegeois, N.J.; Califano, J.A.; Sidransky, D.; Ha, P.K. Quantitative methylation profiles for multiple tumor suppressor gene promoters in salivary gland tumors. PLoS One. 2010;5(5):e10828.
  9. Demokan, S.; Chang, X.; Chuang, A.; Mydlarz, W.K.; Kaur, J.; Huang, P.; Khan, Z.; Khan, T.; Ostrow, K.L.; Brait, M.; Hoque, M.O.; Liegeois, N.J.; Sidransky, D.; Koch, W.; Califano, J.A. KIF1A and EDNRB are differentially methylated in primary HNSCC and salivary rinses. Int J Cancer. 2010 Nov 15;127(10):2351-2359.
  10. Dasgupta, S.; Koch, R.; Westra, W.H.; Califano, J.A.; Ha, P.K.; Sidransky, D.; Koch, W.M. Mitochondrial DNA mutation in normal margins and tumors of recurrent head and neck squamous cell carcinoma patients. Cancer Prev Res (Phila). 2010 Sep;3(9):1205-1211.

Patents

Detection of hypermutable nucleic acid sequence in tissue and body fluids
Patent # 1 6,479,234

p40 protein acts as an oncogene
Patent # 2 6,476,206

Method for detecting cell proliferative disorders
Patent # 3 6,291,163

Detection of neoplasia by analysis of saliva
Patent # 4 6,235,470

Cell cycle regulatory gene
Patent # 5 6,204,374

Nucleic acid mutation detection in histologic tissue
Patent # 6 6,025,127

Detection of hypermutable nucleic acid sequence in tissue
Patent # 7 5,935,787

Cell cycle regulatory gene
Patent # 8 5,908,920

Method of detection of neoplastic cells
Patent # 9 5,856,094

Cell cycle regulatory gene
Patent # 10 5,767,258

Analysis of sputum by amplification and detection of mutant nucleic acid sequences
Patent # 11 5,726,019

Nucleic acid mutation detection by analysis of sputum
Patent # 12 5,561,041

Activities & Honors

Honors

  • National Research Service Award, 1989 - 1991
  • Young Investigators Merit Award, 1992 - 1992
  • Clinician Scientist Award, Johns Hopkins Hospital, 1992 - 1992
  • Foundation for the Promotion of Cancer Research Award (Japan), 1995 - 1995
  • Sarstedt International Research Prize, German Society of Clinical Chemistry, 1997 - 1997
  • Cheng Suen Man Shook Foundation Award, Hong Kong Cancer Institute, 1998 - 1998
  • Walter Hubert Award, British Association of Cancer Research, 1998 - 1998
  • The Alton Ochsner Award Relating Smoking and Health, American College of Chest Physicians, 1998 - 1998
  • The International Union Against Cancer Role of Honour, 1999 - 1999
  • The Israel Cancer Research Fund Osserman Award, 2001 - 2001
  • AACR-Richard and Hinda Rosenthal Foundation Award, 2004 - 2004
  • Toby Comet Award, Bar Ilan University, 2007 - 2007

Memberships

  • American Association for Cancer Research, 1990
  • American Society for Microbiology, 1992
  • American Association for the Advancement of Science, 1992
  • New York Academy of Sciences, 1992
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