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Daniel William Cramer, M.D., Sc.D.

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Overview
I am a clinical epidemiologist whose research has focused mainly on the prevention and early detection of ovarian cancer. I have offered an immunity-based model to explain ovarian cancer pathogenesis and progression involving the mucin (MUC) family of glycoproteins. CA15.3(MUC1) and CA125(MUC16) are important biomarkers for ovarian cancer that normally line the genitourinary, respiratory, and digestive tracts, breast ducts, and peritoneal cavity. Mucins become over expressed during inflammatory, infectious, hormonal, or neoplastic events affecting these tissues and give rise to anti-mucin antibodies. Protective factors like mumps, mastitis, and tubal ligation release tumor-like forms of MUC1 or MUC16, expose them to the immune system, and lead to anti-MUC1 or anti-MUC16 antibodies that protect against ovarian cancer. However, events like endometriosis, uninterrupted ovulation, and cosmetic talc use in genital area lead to chronic exposure to tumor-like mucins, down regulation of immunity, and increased risk for mucin-expressing cancers like ovarian. Cellular immune reactions to the mucins also occur involving binding of mucins to leukocyte subsets to up or down regulate immune responses to tumors or their precursors.

These observations lay the foundation for a new paradigm for viewing ovarian cancer risk factors, mucin tumor markers, and circulating WBC’s in the following way:
1) Levels of mucins are changed not only by a tumor but also by risk factors for the tumor. Associations may be seen in individuals with cancer as well as those with risk factors but no cancer.
2) Early on, there are interactions between mucins and the immune system shown by the existence of anti-mucin antibodies and correlations between serum levels of the mucins or their antibodies and differential white blood cell counts. The latter correlation may partially reflect mucin-binding to specific leukocyte subsets.
3) These interactions not only pertain to MUC1 and MUC16 but may also extend to: other important
glycoprotein tumor markers (CEA, PSA, MUC4); some of the most important risk factors (obesity, smoking, incessant ovulation, and hormone use); and some of the most important cancers (ovarian, breast, colorectal, pancreatic, lung, renal, bladder, and prostate).

My plan for moving this research forward includes development of: efficient standardized assays for anti-mucin antibodies, novel microscopic techniques to quantify the degree of mucin-binding and qualify the cell type to which they are bound, relevant in-vitro and in-vivo experiments to test elements of these hypotheses, and specimen sets that includes viable white cells and serum from normal controls and pretreatment specimens from women with ovarian cancer and benign pelvic tumors. My research has been enabled by the generous participation of cancer cases and controls, support from many colleagues, and nearly continuous funding for this research from the National Cancer Institute since 1978. In 2016, I was awarded an R35 (Outstanding Investigator) grant.

Listed below are relevant papers published within the last 10 years.

Mentoring
Polymorphisms of MUC16 (CA125) and MUC1 (CA15.3) in relation to ovarian cancer risk and survival
Full Time/Year Long, 09/01/12 - 08/31/13

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R35CA197605 (CRAMER, DANIEL WILLIAM) Mar 1, 2016 - Feb 29, 2024
    NIH
    Mucins and immune cell interactions in ovarian cancer pathogenesis & progression
    Role: Principal Investigator
  2. R01CA158119 (CRAMER, DANIEL WILLIAM) Apr 1, 2012 - Mar 31, 2017
    NIH
    Screening and Risk Biomarkers for Ovarian Cancer in EPIC Specimens
    Role: Principal Investigator
  3. R01CA123170 (CRAMER, DANIEL WILLIAM) Aug 18, 2006 - Jun 30, 2012
    NIH
    MUC-1 related cancer immunity: determinants and predictive significance
    Role: Principal Investigator
  4. P50CA105009 (CRAMER, DANIEL WILLIAM) Aug 1, 2004 - Jul 31, 2012
    NIH
    Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE
    Role: Principal Investigator
  5. R01MH069732 (CRAMER, DANIEL WILLIAM) May 13, 2004 - Nov 30, 2009
    NIH
    Risk for New onset of Depression in Perimenopausal Women
    Role: Principal Investigator

Bibliographic
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.