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Sandra Degen, PhD.

Sandra J. F. Degen, PhD

Title

Associate Chair for Academic Affairs;Vice President for Research, University of Cincinnati

Appointment

Professor of Pediatrics, University of Cincinnati College of Medicine

Email

sandra.degen@cchmc.org

Phone

513-636-4816

Fax

513-636-4317

Bio

Sandra J. F. Degen, PhD, received her BA degree in Chemistry from the University of California, San Diego in 1976 and her PhD degree in Biochemistry from the University of Washington in 1982.

Following a two year post-doctoral fellowship at the Friedrich Miescher Institute in Basel, Switzerland, she was appointed as an Assistant Professor of Pediatrics at the University of Cincinnati in 1985. She is presently a tenured Professor of Pediatrics.

The research in Dr. Degen's laboratory focused on two areas of interest that includes blood coagulation and cancer research.

Specifically, research efforts concentrated on studying the regulation and biology of prothrombin, a protein involved in the blood coagulation process.

This laboratory was also responsible for identifying a new growth factor call hepatocyte growth factor-like protein and has been actively studying its biological properties along with those of its tyrosine kinase receptor called Ron.

Dr. Degen has three patents in this area. Dr. Degen has had continuous grant support since she received her first academic position, and until 2006 was principal investigator on two National Institutes of Health (NIH) grants.

Dr. Degen's honors and awards include being selected as a Pew Scholar in the Biomedical Sciences supported by the Pew Memorial Trust, being awarded an Established Investigatorship from the American Heart Association, serving as a regular member of the Hematology II study section at the NIH and being selected to attend the Executive Leadership in Academic Medicine Program for Women in 1997.

Most recently she was selected to participate in the Science and Society Institute sponsored by the Pew Scholars Program.

Dr. Degen's administrative responsibilities include being the Associate Chair for Academic Affairs for the Department of Pediatrics, the Chair of the Department of Pediatrics Reappointment, Promotion and Tenure Committee and Vice President for Research at the University of Cincinnati.

Dr. Degen is responsible for overseeing faculty development and the graduate programs within the department.

There are over 450 full-time faculty within the department and over 200 volunteer faculty.

For the University of Cincinnati, she is responsible for all research compliance activities, the animal research program, sponsored research services, sponsored program accounting, entrepreneurial affiars, the intellectual property office, research educational programs and regional, state and federal advocacy with regard to research. More information can be found at the web site for the Office of Research.

Dr. Degen's past responsibilities have included being Director of the Graduate Program in Molecular and Developmental Biology, Chair of the Committee on Graduate Education at the College of Medicine of the University of Cincinnati, and Chair of the Research Committee for the American Heart Association, Ohio-West Virginia Affiliate.

Dr. Degen serves on the Board of Directors of Bio/Start, the Ohio Aerospace Institute, Techsolve and the Oak Ridge Associated Universities.

Dr. Degen has had a long-term interest in graduate education and in mentoring both faculty and students.

Credentials

BA: Chemistry, University of California, San Diego, 1976.

PhD: Biochemistry, University of Washington, Seattle, WA, 1982.

Fellowship: Post-doctoral fellowship at the University of Washington in Seattle, WA, 1982-83; post-doctoral Fellowship at the Friedrich Meischer Institute in Basel, Switzerland, 1983-1985.

Awards and Honors

  • NIH Metabolic Pathology study section, Ad Hoc Member, 2002-2005
  • Research Committee, American Heart Association, National, 2002-2005
  • NIH Special Emphasis Panel, ZRG-1 SSS-1, 2002
  • Women's Leadership Committee, American Heart Association, National, 2002-2004
  • NIH Hematology II Study Section, Ad Hoc Member, 2003
  • NIH Special Emphasis Panel, ZRG CAMP, 2003
  • Elected Fellow of the Graduate School, University of Cincinnati, 2003-present
  • Nominee for Outstanding Woman at Cincinnati Children's Hospital, 2004
  • Board of Trustees and Executive Committee, BIO/START, 2005
  • Howard Hughes Medical Institute/Burroughs Welcome Foundation Partners in Scientific Management Program, 2004-2005
  • Board of Directors, TechSolve, 2005-present
  • Founders Award, Womens Faculty Association, Cincinnati Children's Hospital Medical Center, 2005
  • Recognition Award in Thrombosis, American Heart Association, National Center, Council on Arteriosclerosis, Thrombosis and Vascular Biology, 2005
  • NIH Special Review Panel, Liver Procurement Contract, 2006
  • Elected Vice Chair, Council of Sponsoring Institutions, Oak Ridge Associated Universities (will become Chair from 2009-2011), 2007-2009
  • Board of Directors, Oak Ridge Associated Universities, 2007-present
  • Executive Committee, Board of Directors, Oak Ridge Associated Universities, 2007-present

Research

Basic science research in the areas of blood coagulation and cancer.

Dr. Sandra Degen's laboratory was involved in studying the regulation of expression of proteins involving blood coagulation and in growth control. These proteins are structurally related but have different biological functions.

One of these proteins, prothrombin, has diverse biological roles. It is crucial for the clotting of blood and in the anticoagulation process, in the stimulation of platelets to undergo a shape change, causes mitogenesis in fibroblasts, is chemotactic for macrophages, and is involved in the regulation of proliferation of endothelial cells and possibly other cell types.

Dr. Degen's lab generated mice that are deficient in prothrombin in order to study the role of prothrombin in development and other biological processes.

Approximately half of the prothrombin-deficient mice die in utero, due to bleeding events, between embryonic days 9 and 10 while the remainder die soon after birth from abdominal bleeding.

A long-term goal of this project is to generate mice carrying a mutant prothrombin gene for specific structure-function studies.

An extensive number of site-directed mutants of prothrombin have been studied by in vitro techniques. In this manner, the mutant form of the protein can be studied in vivo and in its various biological contexts.

Since prothrombin has roles in both the coagulation and anticoagulation of blood, its regulation is crucial to bleeding and thrombosis. These studies will give further insight into these opposing roles. These mice are also being used to further understand the role of brain-specific expression of prothrombin.

Dr. Degen's lab also worked on hepatocyte growth factor-like protein (HGFL) and its membrane tyrosine kinase receptor (Ron). HGFL and Ron have been found to have diverse biological properties based on in vitro assays.

These functions include involvement in the activation of macrophage, invasiveness of trophoblasts, motility of keratinocytes and bone resorption of osteoclasts.

They successfully ablated the genes for HGFL and Ron (separately) in mice. HGFL null mice are born and appear to be normal until about 3 months of age where they start to have liver and possibly kidney problems.

Deletion of the Ron gene is embryonic lethal during the peri-implantation time of development.

Other studies included the identification of additional HGF-like growth factors that might compensate for HGFL in the HGFL-deficient mice, especially with regard to implantation; identification of the biological properties of HGFL and Ron later in development and in the adult mouse using the cre-lox system to generate mice lacking Ron in specific organ systems; determination of the biological properties that result from the constitutive expression of Ron; structure-function studies on Ron; and determination of the role of Ron and HGFL during implantation.

Research Grants and Contracts

Current

Charlotte R. Schmidlapp Trust (Fifth Third Bank), "Center for Career Development of Women in Academic Pediatrics," (S.J.F. Degen, PI, 5% effort), 4/05 – 3/09, Total Direct Costs = $1,500,000.

Completed

12/98 - 11/02
NIH (HL57530) "Functional Mapping and Protein Engineering of Thrombin," (L Leung, PI; SJF Degen, Co PI, 5% effort), Total Direct Costs = $994,772

5/01 - 4/05
NIH (DK58182) "The biology of Ron, the HGF-like protein receptor," (SJF Degen, PI, 20% effort), Total Direct Costs = $765,000

12/01-11/05
NIH (HL58103) "Characterization and Use of Prothrombin Deficient Mice," (SJF Degen, PI, 25% effort), Total Direct Costs = $950,000

Publications, Most Recent

Sandra Degen's publications as listed by PubMed.

Sun WY, Burkart MC, Holahan JR, Degen SJF. Prothrombin San Antonio: A single amino acid substitution at one of the Factor Xa activation sites (Arg320 to His) results in dysprothrombinemia. Blood 95:711-714 (2000).


Sun WY, Smirnow D, Jenkins, ML, Degen, SJF. Prothrombin Scranton: Substitution of an amino acid residue involved in the binding of Na+ (LYS-556 to THR) leads to dysprothrombinemia.Thromb. Haem. 85:651-654 (2001).

Waltz SE, Eaton L, Toney-Earley K, Hess KA, Ihlendorf JR, Kaestner KH, Degen SJF. Ron- mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses.J. Clin. Invest. 108:567-576 (2001).

Peace BE, Hughes MJ, Degen, SJF, Waltz SE. Point mutations and overexpression of Ron induce transformation, tumor formation and metastasis.Oncogene 20:6142-6151 (2001).


McDowell SA, Mallakin A, Bachurski, C.J. Toney-Earley K, Prows DR, Bruno T, Kaestner, KH, Witte DP, Melin-Aldana H, Degen SJF, Leikauf GD, Waltz SE. The role of the receptor tyrosine kinase Ron in nickel-induced acute lung injury. Amer J Resp Cell & Mol Biol 26:99-104 (2002).

Degen SJ. Women scientists should be role models. OpEd in Cincinnati Enquirer, April 15, 2002.

Leonis MA, Toney-Earley K, Degen SJF, Waltz SE. Deletion of the Ron receptor tyrosine kinase domain in mice provides protection from endotoxin-induced acute liver failure.Hepatology 36:1053-1060 (2002).

Sun, W.Y., Coleman, M.J., Witte, D.P. and Degen, S.J.F. Rescue of prothrombin-deficiency by transgene expression in mice.Thrombosis & Hemostasis 88, 984-991 (2002).

Hess, K.A., Waltz, S.E., Chan, E.L. and Degen, S.J.F. Receptor tyrosine kinase Ron is expressed in mouse reproductive tissues during embryo implantation and is important in trophoblast cell function.Biol Reprod 68, 1267-1275 (2003).

Wetzel, C.C., Degen, S.J.F. and Waltz, S.E. cis-Acting elements in the hepatocyte growth factor-like protein gene regulate kidney and liver-specific expression in mice.DNA and Cell Biology 22, 293-301 (2003).

Hess, K.A., Waltz, S.E., Toney-Earley, K. and Degen, S.J.F. The receptor tyrosine kinase Ron is expressed in the mouse ovary and regulates inducible nitric oxice synthase levels and ovulation.Fertility and Sterility 80S2, 747-754 (2003).

Peace, B.E., Hill, K.J., Degen, S.J.F. and Waltz, S.E. Cross-talk between the receptor tyrosine kinases Ron and epidermal growth factor receptor.Experimental Cell Res 289, 317-325 (2003).

Wu, J., Wang, Y., Xiao, W., Meyer, K.b., Schmidt, K., Morris, R.E., Degen, S.J.F. and La Barbera, A.R. Assessment of recombinant porcine follicle-stimulating hormone receptor using a novel polyclonal ectodomain antibody.Endocrine Res. 30, 269-285 (2004).

Kahn, J.A., Degen, S.J.F., Mansour, M., Goodman, E., Zeller, M. H., Laor, T., Lanphear, N. E. and Boat, T. F. Pediatric faculty members' attitudes about part-time faculty positions and policies to support part-time faculty: A study at one medical center. Academic Medicine 80, 931-939 (2005).

Wetzel, C.C., Leonis, M.A., Dent, A., Olson, M.A., Longmeier, A.M., Ney, P.A., Boivin, G.P., Kader, S.A., Caldwell, C.C., Degen, S.J.F., and Waltz, S.E. Short Form Ron Receptor Is Required For Normal IFN-gamma Production In Concanavalin A-Induced Acute Liver Injury. American J. Physiology: GI and Liver Physiology 292, G253-261 (2007).

Professional Organization Memberships

Teaching

1994-present
NIH Training Grant (HL07752), "Pulmonary and Cardiovascular Development," (JA Whitsett, PI; S Degen on Training Faculty and Executive Committee).

7/95-present
NIH Training Grant (DK07727), "Pediatric Gastroenterology and Nutrition Training Grant (M Cohen, PI; S Degen on Executive Committee and Training Faculty).

7/96-6/00
NIH Training Grant (HL07825), "Cardiovascular and Molecular Biology of the Young," (J Robbins, PI; S Degen on Training Faculty).

7/96-present
NIH Training Grant (HL07382), "Training in Cardiovascular Biology," (A Schwartz, PI; S Degen on Training Faculty).

11/99-present
NIH Training Grant (HD07463), "Training in Developmental and Perinatal Endocrinology," (S Handwerger, PI; S Degen on Training Faculty).

7/01-present
NIH Training Grant (CA59268), "Regulation of Cellular Growth and Differentiation," (S Khan, PI; S Degen on Training Faculty).

4/01-3/05
NIH Training Grant (ES10957), "Molecular Epidemiology in Environmental Health," (G LeMasters, PI; S Degen on Training Faculty and on Admissions, Recruitment and Retention Committee).

Presentations

Hepatocyte Growth Factor-like Protein and Its Receptor: A Search for Their Biological Function. Wright State University, Department of Biochemistry and Molecular Biology; 1997 Oct 31; Dayton, Ohio.

Expression of the Receptor Tyrosine Kinase Ron is Required for Embryonic Development. The FASEB Meeting on Mechanisms of Liver Growth and Differentiation in Health and Disease; 1998 July 11-16; Snowmass, Colorado.

Prothrombin-Structure and Function. A Celebration Honoring Virginia Donaldson, Children's Hospital Medical Center; 1998 May 16; Cincinnati, Ohio.

The Puffer Fish and What It Can Tell Us. Developmental Biology Cutting Edge Seminar Series, Children's Hospital Research Foundation; 1998 Nov 9; Cincinnati, Ohio.

Expression of the Receptor Tyrosine Kinase Ron is Required for Embryonic Development. Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati; 1999 Jan 19; Cincinnati, Ohio.

Novel Genes Involved in Embryonic and Cellular Invasion. Molecular Medicine Research Seminar Series, Children's Hospital Research Foundation; 1999 Dec 13; Cincinnati, Ohio.

"Transgenic Approaches to Correcting Prothrombin Deficiency in Mice" presented at the FASEB Meeting on "Vascular Biology and Thrombin" Whitefish, Montana, June 9-14, 2001.

"The Biology of the Ron Tyrosine Kinase" presented at the FASEB Meeting on "Growth Factor Receptor Tyrosine Kinases in Mitogenesis, Morphogenesis and Tumorigenesis" Snowmass, CO, August 4-9, 2001.

Stipend and benefit support is available to qualified candidates through NHLBI Training Grant: T-32 HL07382-30: "Training In Cardiovascular Biology", Dr. Arnold Schwartz, Principal Investigator.

Patents

  • U.S. Patent No. 5,315,000, May 24, 1994
    Degen, SJ
    Gene Encoding for a L5/3 Growth Factor and its cDNA
  • U.S. Patent No. 5,606,029, February 25, 1997
    Degen, SJ
    Gene for a Growth Factor and its cDNA and Protein
  • U.S. Patent No. 7,235,523, June 26, 2007
    Waltz SE, Leonis MA, Degen SJ
    Methods for the Treatment of Hepatic Disorders

Related Areas

This person works in these other areas at Cincinnati Children's Hospital Medical Center: