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Alan Keith Meeker, M.A.T., Ph.D.

Photo of Dr. Alan Keith Meeker, M.A.T., Ph.D.
  • Director, Oncology Tissue Services, Johns Hopkins Sidney Kimmel Comprehensive Care Center
  • Associate Professor of Pathology

Research Interests

Cancer; Quantitative fluorescence microscopy; Molecular pathology; Urology; Prostate cancer; Cancer biology; Telomeres; Pathology; Biology of aging; Cellular Senescence ...read more

Background

Dr. Alan Meeker is an assistant professor of pathology, oncology and urology at the Johns Hopkins School of Medicine. Dr. Meeker co-directs the Immuohistochemistry Laboratory of Johns Hopkins Oncology Tissue Services and serves on the faculty of the Graduate Program in Pathobiology. He joined the Hopkins faculty in 2006.

Dr. Meeker has spent his career studying chromosomal structures called telomeres. Telomeres that are too short appear to contribute to the genetic instability thought to cause the development and progression of many types of cancer. They are also believed to be related to human aging and the age-related phenomenon of cellular senescence.

Dr. Meeker primarily studies the relationship between shortened telomeres and prostate cancer. He was part of a Johns Hopkins team that developed a new quantitative fluorescence microscopy technique to measure telomere lengths directly in archival tissues.

In addition to the many academic papers he has published, Dr. Meeker also contributed to the books Prostate Cancer: Biology, Genetics, and the New Therapeutics as well as Campbell-Walsh Urology, 10th and 11th ed.

...read more

Titles

  • Director, Oncology Tissue Services, Johns Hopkins Sidney Kimmel Comprehensive Care Center
  • Co-director, Cell Imaging Core, Johns Hopkins Sidney Kimmel Comprehensive Care Center
  • Associate Professor of Pathology
  • Associate Professor of Oncology
  • Associate Professor of Urology

Departments / Divisions

Centers & Institutes

Education

Degrees

  • Ph.D., Johns Hopkins University School of Medicine (Maryland) (2001)
  • M.A.T., Johns Hopkins University (Maryland) (1991)
  • B.S., Florida Institute of Technology (Florida) (1983)

Additional Training

The Johns Hopkins University School of Medicine, Baltimore, MD, 2005, Postdoctoral research fellow

Research & Publications

Research Summary

Dr. Meeker has spent his career studying chromosomal structures called telomeres. Defective telomeres – specifically, those that are too short – appear to contribute to the genetic instability thought to cause the development and progression of many types of cancer.

Clearly seen at the chromosomal level in epithelial cancers such as prostate and breast cancers, the molecular mechanisms responsible for chromosome destabilization during carcinogenesis and progression have remained largely unknown.

To better understand these mechanisms, Dr. Meeker’s team worked with the DeMarzo Laboratory to develop a novel quantitative fluorescence microscopy technique to measure telomere lengths directly in archival tissues.

The team found that telomeres are indeed abnormally short in most microscopic precursor lesions in epithelial cancers – including those of the bladder, breast, cervix, colon, esophagus, gall bladder, oral cavity and prostate.

The belief is that those lesions are at risk of progressing to fully invasive carcinomas—and that telomere shortening may be useful in diagnosing cancer, as an intermediate endpoint marker in chemoprevention studies, and as a valid prevention target in its own right.

The telomere-length assay, which features single-cell resolution, can be used to test the hypothesized link between telomere shortening and human aging.

Lab

The primary focus of my research activities for the last 2 decades has been on cancer-associated abnormalities in telomere biology. My research discoveries provide significant supporting data that telomere biology plays multiple important roles in the disease process. For example, using a novel tissue-based assay I developed while a postdoc in the laboratory of Dr. Angelo De Marzo, we found that the majority of pre-malignant lesions display severe telomere shortening; thus, this genomic abnormality arises very early in the disease process, likely contributing significantly to the process of malignant transformation by instigating chromosomal instability. Other key discoveries in the lab include the finding of widespread telomere shortening in the breast epithelium of normal women, the finding that tissue-based telomere length measurements are significantly associated with cancer risk and clinical outcomes among prostate cancer patients, and the discovery of a strong association between recurrent, inactivating mutations in the ATRX or DAXX genes and cancers utilizing a telomerase-independent telomere maintenance mechanism termed ALT. In addition to my primary focus on telomere biology I also perform studies on in situ tumor biomarker development and in vitro drug screening for anti-cancer agents, and maintain an interest in the biology of aging and cellular senescence, particularly how this may relate to cancer risk and progression.

Lab Website: Meeker-Heaphy Lab
Core Facility: SKCCC Cell Imaging

Clinical Trials

Learn more about clinical trials at the Johns Hopkins Kimmel Cancer Center.

Selected Publications

Heaphy CM, de Wilde RF, Jiao Y, Klein AP, Edil BH, Shi C, Bettegowda C, Rodriguez FJ, Eberhart CG, Hebbar S, Offerhaus GJ, McLendon R, Rasheed BA, He Y, Yan H, Bigner DD, Oba-Shinjo SM, Marie SK, Riggins GJ, Kinzler KW, Vogelstein B, Hruban RH, Maitra A, Papadopoulos N, Meeker AK. Altered Telomeres in Tumors with ATRX and DAXX Mutations. Science. 2011;22:333; 425. PMID: 21719641 PMCID: PMC3174141

Heaphy CM, Subhawong AP, Hong SM, Goggins MG, Montgomery EA, Gabrielson E, Netto GJ, Epstein JI, Lotan TL, Westra WH, Shih IeM, Iacobuzio-Donahue CA, Maitra A, Li QK, Eberhart CG, Taube JM, Rakheja D, Kurman RJ, Wu TC, Roden RB, Argani P, De Marzo AM, Terracciano L, Torbenson M, Meeker AK. Prevalence of the Alternative Lengthening of Telomeres (ALT) Telomere Maintenance Mechanism in Human Cancer Subtypes. Am Jol Pathology. 2011;179(4):1608-1615. PMID: 21888887

Lovejoy CA, Li W, Reisenweber S, Thongthip S, Bruno J, de Lange T, De S, Petrini JH, Sung PA, Jasin M, Rosenbluh J, Zwang Y, Weir BA, Hatton C, Ivanova E, Macconaill L, Hanna M, Hahn WC, Lue NF, Reddel RR, Jiao Y, Kinzler K, Vogelstein B, Papadopoulos N, Meeker AK. Loss of ATRX, genome instability, and an altered DNA damage response are hallmarks of the alternative lengthening of telomeres pathway. PLoS Genet. 2012; 8(7):e1002772. Epub 2012 Jul 19

Heaphy CM, Yun GS, Peskoe SB, Joshu CE, Lee TK, Giovannucci E, Mucci LA, Kenfield SA, Stampfer MJ, Hicks JL, De Marzo AM, Platz EA, Meeker AK. Prostate Cancer Cell Telomere Length Variation and Stromal Cell Telomere Length as Prognostic Markers for Metastasis and Death. Cancer Discovery. 2013;Oct; 2(10):1130-41. PMID:23779129

Graham, M, Meeker, A.K. The role of telomeres and telomerase in prostate cancer development and therapy. Nature Reviews Urology. 2017 Jul 4. [Epub ahead of print]

Contact for Research Inquiries

Department of Pathology
411 N. Caroline Street

Email me

Academic Affiliations & Courses

Graduate Program Affiliation

Pathobiology Graduate Program, Department of Pathology

Cellular and Molecular Medicine, Johns Hopkins School of Medicine

Biochemistry and Molecular Biology Graduate Program, Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health

 

Courses and Syllabi

  • Stem Cells and the Biology of Aging and Disease (PH.120.627)
    lecture
  • Cancer Biology (PH.120.624)
    lecture
  • Phenotyping for Functional Genetics (ME:680.712)
    multiday workshop/lecture+lab
  • Biological Basis of Aging (260.665.01)
  • Stem Cells and the Biology of Aging and Disease (AS.020.337)
    lecture
  • Introduction To The Human Body: Anatomy, Histology and Physiology (ME: 800.702)
    lecture/lab

Activities & Honors

Honors

  • The Paul Ehrlich Research Award, Johns Hopkins School of Medicine, Baltimore, MD.
  • AACR-AFLAC Scholar-in-Training Awards, American Association for Cancer Research and AFLAC
  • Best Scientific Session for "“Improved Software for Quantitative Analysis of Fluorescence Microscopy Images.”, Advancing Practice Instruction and Innovation through Informatics (APIII)
  • ASIP Merit Award, American Society for Investigative Pathology
  • Young Investigator Award, David Koch/Prostate Cancer Foundation
  • AACR Team Science Award, American Association for Cancer Research (AACR)

Memberships

  • American Association for Cancer Research

    Active member.

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  • American Urologic Association

    Affiliate Member

Videos & Media

Lectures and Presentations

  • Telomere Dynamics, Genetic Instability and Cancer
    Podium talk, Baltimore Area Repair Symposium, Baltimore, MD (03/10/2012)
    Baltimore Area Repair
  • Exomic Sequencing in Pancreatic NETs: Potential Clinical Applications
    Podium talk, VIII Simposio Internacional GETNE, Seville, Spain (05/14/2012)
    GETNE (Grupo Espanol de Tumores Neuroendocrinos)
  • Epigenetics of Pancreatic Neuroendocrine Tumors.
    Podium talk, European Neuroendocrine Tumor Society 2013 Annual Conference, Barcelona, Spain (04/21/2013)
    European Neuroendocrine Tumor Society (ENETS)
  • Telomere Translation: Moving Telomere Research From Bench to Bedside to Benefit Cancer
    Podium talk, International Conference on Genomic Medicine, Baltimore, MD. (02/10/2017)
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