Sandra J. F. Degen

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Sandra J.F. Degen
Sandra-2016.jpg
Bornc. 1955 (age 65–66)
Glendale, California
NationalityAmerican
Alma mater University of California, San Diego
University of Washington
Friedrich Miescher Institute
Known forCharacterizing prothrombin cDNA, discovery of hepatocyte growth factor-like protein
AwardsPew Scholar in the Biomedical Sciences, University of Cincinnati Faculty Achievement Award, Special Recognition in Thrombosis, WE Celebrate Award Finalist and Runner-up for Women of the Year 2014
Scientific career
FieldsBiochemistry, molecular genetics
Institutions University of Cincinnati

Sandra J. F. Degen (born c. 1955) [1] is an American biochemist, molecular geneticist and Professor Emerita at the University of Cincinnati Children's Hospital Medical Center in the Department of Pediatrics. Degen was a professor at the University of Cincinnati for over thirty years, where she led a research program focused on probing the biology underlying blood coagulation, growth factors, and growth control. Her lab discovered a novel growth factor called hepatocyte growth factor-like protein. Degen is a member of several national societies and is an elected Fellow of the American Association for the Advancement of Science (AAAS).

Contents

Early life and education

Degen was born in 1955 in Glendale, California. [1] She grew up just outside of Los Angeles, in the San Fernando Valley of California. [1] Her father was a scientist and her mother was a seamstress and she was one of four children. [1] It was only once Degen started her undergraduate degree that she realized she wanted to pursue a career in science. [1] First deciding to focus her studies in mathematics, Degen pursued her Bachelor of Arts at the University of California, San Diego. [2] She switched her major to Chemistry after experiencing a challenging chemistry class and was excited to learn more. [1] In her final year at UCSD, she worked in the laboratory of Russell F. Doolittle studying fibrinogen, a blood clotting factor. [1] She became an author on several papers through her undergraduate work, specifically characterizing the amino acid sequences of the alpha chain of fibrinogen. [3] She graduated in 1976 with a degree in Chemistry. [1]

Following her undergraduate degree, Degen pursued a Ph.D. in Biochemistry at the University of Washington in Seattle, Washington. [2] She worked in Earl Davie's lab studying human prothrombin, another blood protein involved in coagulation. [1] She completed her Ph.D. in 1982 and moved to Switzerland to complete her postdoctoral work at the Friedrich Miescher Institute in Basel, Switzerland. [2] During her two-year postdoc, Degen worked under the mentorship of Edward Reich studying the plasminogen activator gene. [4] Degen completed her postdoctoral training in 1985. [1]

Career and research

In 1985, Degen was recruited to the University of Cincinnati in Cincinnati, Ohio where she became an Assistant Professor of Pediatrics at the Children's Hospital Medical Center. [1] In 1992 she was promoted to Associate Professor with tenure and finally received her Full Professorship in 1997. [2] In 2004, Degen was appointed the acting vice president for research at the University of Cincinnati. [2] Degen also held appointments as the Associate Chair of Academic Affairs for the Department of Pediatrics, and was the Chair of the Department of Pediatrics Reappointment, Promotion, and Tenure Committee.[ citation needed ] She held her full professorship until 2015, at which point she became a professor emerita for the University of Cincinnati. [5]

While at Cincinnati, Degen was the principal investigator of a lab studying the regulation and biology of the blood coagulation protein, prothrombin. [2] Her lab discovered a novel growth factor called hepatocyte growth factor-like protein and they extensively studied the functions of this growth factor as well as its tyrosine kinase receptor, Ron. [2] During her tenure at Cincinnati, Degen and her lab filed three patents for their growth factory discoveries and their use in treating hepatic disorders. [6]

Beyond her research, Degen has actively contributed to bettering the academic environment for women and promoting gender equity in science. [7] She help start the Women Scholars Program and Young Women Scholars Program at the University of Cincinnati Children's Hospital which served to support the career development of women across career stages. [7] Degen also showed her commitment to inspiring the next generation of young scientists by supporting development programs for high schoolers and conducting annual science career days. [8] For her work, she was named Woman of the Year Runner-Up by the Cincinnati Youth Collaborative in 2014. [7]

Characterization of prothrombin cDNA

During her graduate studies, Degen and her colleagues were the first to isolate and characterize complementary DNA (cDNA) coding for both bovine and human prothrombin. [9] Prothrombin is a coagulation factor critical in the initial steps of blood clotting. [9] They prepared the human prothrombin from human liver mRNA. [9] Prior to their characterization, only the amino acid sequences had been reported, so they compared their cDNA sequences to the previously reported amino acid sequences and found several differences in the predicted amino acid structure from their cDNA. [9] Several years later, after isolating cDNA for prothrombin from mice, they were able to characterize the complete prothrombin cDNA and from this predict the complete amino acid sequence of the prothrombin protein in mice. [10] They subsequently mapped the gene to the mouse chromosome 2. [10]

Characterization of human tissue plasminogen activator gene

During her postdoctoral work, Degen led a team to characterize the human tissue plasminogen activator (t-PA) gene. [11] Human t-PA is a protein implicated in the breakdown of blood clots and is expressed in many tissues as well as by tumors. [11] Degen's characterization of the complete nucleotide sequence was prompted by the desire to study the complex genetic regulation of t-PA expression and the implications this has in tumor growth. [11] Their analysis highlighted several reading frames of the gene which prompted further investigation of the various gene products possible. [11]

Characterization of hepatocyte growth factor-like protein

Early into her career at the University of Cincinnati, Degen led a team towards the discovery of a novel kringle-containing protein in mice which they called hepatocyte growth factor-like (HGFL) protein. [12] They sequenced, for the first time, the gene and complementary DNA and found that it shared the same structural domains as hepatocyte growth factor, hence their name choice. [12]  They found that the gene expression was restricted to the liver via in situ hybridization analysis and thus despite the similarities to hepatocyte growth factor, its expression profile in primarily hepatocytes allowed Degen to conclude that it was in fact a novel protein. [12]

Following this discovery, Degen and her team characterized the functional domains of the protein to understand its biological importance. [13] Since HGFL had been found to play a role in stimulating mouse resident peritoneal macrophages and inducing cellular proliferation, motility, and apoptosis, Degen and her team sought to probe the function of the specific domains of the protein. [13] They caused site-directed and deletion mutations in cDNA that coded for the protein and found that the heavy chain may play an important role in its function while the light chain may play a role in binding to its receptor, Ron. [13] They later disrupted the HGFL gene in mice rendering loss of the HGFL protein to probe its impact on cellular and system function. [14] They found that, though loss of HGFL delayed macrophage activation, it was not essential for embryogenesis, fertility, nor wound healing. [14] When Degen and her team next probed the importance of the HGFL receptor, Ron, in biological functions, they found that ablation of the tyrosine kinase domain of Ron caused altered ability to regulate nitric oxide as well as enhanced tissue damage following cell-mediated inflammation. [15]  Next, they probed the effects of Ron tyrosine kinase domain deletion on mouse reproduction and found that it led to decreases in ovulation of oocyte complexes as well as increased levels of induced nitric oxide synthase (iNOS) before and after ovulation. [15] They concluded that the increase in iNOS which leads to an increase in nitric oxide is likely the cause of the decreased ovulation rates. [15]

Awards and honors

Select publications

Personal

Degen is married to Jay L. Degen, who also held a professorship at the University of Cincinnati and studied hemoglobinopathies. The Degens have one daughter. [21]

Related Research Articles

Thrombin Enzyme in humans

Thrombin is a serine protease, an enzyme that, in humans, is encoded by the F2 gene. Prothrombin is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions.

Factor XII

Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme of the serine protease class. In humans, factor XII is encoded by the F12 gene.

Plasmin

Plasmin is an important enzyme present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.

Osteonectin

Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the SPARC gene.

Annexin A2

Annexin A2 also known as annexin II is a protein that in humans is encoded by the ANXA2 gene.

Interleukin 8 receptor, beta

Interleukin 8 receptor, beta is a chemokine receptor. IL8RB is also known as CXCR2, and CXCR2 is now the IUPHAR Committee on Receptor Nomenclature and Drug classification-recommended name.

STK4

Serine/threonine-protein kinase 4 is an enzyme that in humans is encoded by the STK4 gene.

FGF7

Keratinocyte growth factor is a protein that in humans is encoded by the FGF7 gene.

ST14

Suppressor of tumorigenicity 14 protein, also known as matriptase, is a protein that in humans is encoded by the ST14 gene. ST14 orthologs have been identified in most mammals for which complete genome data are available.

FGF10

Fibroblast growth factor 10 is a protein that in humans is encoded by the FGF10 gene.

ZNF148

Zinc finger protein 148 is a protein that in humans is encoded by the ZNF148 gene.

SERPINE2

Glia-derived nexin is a protein that in humans is encoded by the SERPINE2 gene.

ETV1

ETS translocation variant 1 is a protein that in humans is encoded by the ETV1 gene.

MST1

Macrophage-stimulating protein (MSP), also known as hepatocyte growth factor-like protein, is a protein that in humans is encoded by the MST1 gene.

NFE2L1

Nuclear factor erythroid 2-related factor 1 (Nrf1) also known as nuclear factor erythroid-2-like 1 (NFE2L1) is a protein that in humans is encoded by the NFE2L1 gene. Since NFE2L1 is referred to as Nrf1, it is often confused with nuclear respiratory factor 1 (Nrf1).

<i>DBP</i> (gene)

D site of albumin promoter binding protein, also known as DBP, is a protein which in humans is encoded by the DBP gene.

SEP15

15 kDa selenoprotein is a protein that in humans is encoded by the SEP15 gene. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.

LRIG1

Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene. It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR family and with MET and RET.

MAFK

Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.

Formyl peptide receptor 1

Formyl peptide receptor 1 is a cell surface receptor protein that in humans is encoded by the formyl peptide receptor 1 (FPR1) gene. This gene encodes a G protein-coupled receptor cell surface protein that binds and is activated by N-Formylmethionine-containing oligopeptides, particularly N-Formylmethionine-leucyl-phenylalanine (FMLP). FPR1 is prominently expressed by mammalian phagocytic and blood leukocyte cells where it functions to mediate these cells' responses to the N-formylmethionine-containing oligopeptides which are released by invading microorganisms and injured tissues. FPR1 directs these cells to sites of invading pathogens or disrupted tissues and then stimulates these cells to kill the pathogens or to remove tissue debris; as such, it is an important component of the innate immune system that operates in host defense and damage control.

References

  1. 1 2 3 4 5 6 7 8 9 10 11 "Sandra J. F. Degen | Science History Institute | Center for Oral History". oh.sciencehistory.org. Retrieved May 14, 2020.
  2. 1 2 3 4 5 6 7 8 9 10 "Degen Named Acting Vice President for Research at UC". UC.edu. Retrieved May 13, 2020.
  3. ↑ Sheppard, R. C. (October 31, 2007). Amino Acids, Peptides and Proteins: Volume 10. Royal Society of Chemistry. ISBN   978-1-84755-735-3.
  4. ↑ Degen, S. J.; Rajput, B.; Reich, E. (May 25, 1986). "The human tissue plasminogen activator gene". The Journal of Biological Chemistry. 261 (15): 6972–6985. doi: 10.1016/S0021-9258(19)62711-0 . ISSN   0021-9258. PMID   3009482.
  5. 1 2 Trager2017-06-06T14:46:00+01:00, Rebecca. "Older researchers crowding out younger ones". Chemistry World. Retrieved May 14, 2020.
  6. ↑ "Methods for the treatment of hepatic disorders". scienceon.kisti.re.kr (in Korean). Retrieved May 14, 2020.
  7. 1 2 3 4 "Board Member Sandra Degen: Woman of Year Runner-Up". Cincinnati Youth Collaborative. December 11, 2014. Retrieved May 14, 2020.
  8. 1 2 "Head of Cincinnati Children's "New Scientist Pipeline" Awarded AAAS Fellowship". www.cincinnatichildrens.org. Retrieved May 14, 2020.
  9. 1 2 3 4 Degen, Sandra J. Friezner; MacGillivray, Ross T. A.; Davie, Earl W. (April 26, 1983). "Characterization of the complementary deoxyribonucleic acid and gene coding for human prothrombin". Biochemistry. 22 (9): 2087–2097. doi:10.1021/bi00278a008. ISSN   0006-2960. PMID   6305407.
  10. 1 2 Degen, S. J.; Schaefer, L. A.; Jamison, C. S.; Grant, S. G.; Fitzgibbon, J. J.; Pai, J. A.; Chapman, V. M.; Elliott, R. W. (September 1990). "Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2". DNA and Cell Biology. 9 (7): 487–498. doi:10.1089/dna.1990.9.487. ISSN   1044-5498. PMID   2222810.
  11. 1 2 3 4 Degen, S. J.; Rajput, B.; Reich, E. (May 25, 1986). "The human tissue plasminogen activator gene". Journal of Biological Chemistry. 261 (15): 6972–6985. doi: 10.1016/S0021-9258(19)62711-0 . ISSN   0021-9258. PMID   3009482.
  12. 1 2 3 Bezerra, J. A.; Witte, D. P.; Aronow, B. J.; Degen, S. J. (August 1993). "Hepatocyte-specific expression of the mouse hepatocyte growth factor-like protein". Hepatology (Baltimore, Md.). 18 (2): 394–399. ISSN   0270-9139. PMID   8340069.
  13. 1 2 3 Waltz, Susan E.; McDowell, Susan A.; Muraoka, Rebecca S.; Air, Ellen L.; Flick, Leah M.; Chen, Ying-Qing; Wang, Ming-Hai; Degen, Sandra J. Friezner (November 28, 1997). "Functional Characterization of Domains Contained in Hepatocyte Growth Factor-like Protein". Journal of Biological Chemistry. 272 (48): 30526–30537. doi: 10.1074/jbc.272.48.30526 . ISSN   0021-9258. PMID   9374547.
  14. 1 2 "Biological effects of targeted inactivation of hepatocyte growth factor- like protein in mice". ResearchGate. Retrieved May 14, 2020.
  15. 1 2 3 Waltz, Susan; Eaton, Laura; Toney-Earley, Kenya; Hess, Karla; Peace, Belinda; Ihlendorf, Jeffrey; Wang, Ming-Hai; Kaestner, Klaus; Degen, Sandra (September 1, 2001). "Ron-mediated cytoplasmic signaling is dispensable for viability but is required to limit inflammatory responses". The Journal of Clinical Investigation. 108 (4): 567–76. doi:10.1172/JCI11881. PMC   209396 . PMID   11518730.
  16. ↑ Brunsman, Barrett J. (June 12, 2015). "'Remarkable scientists' at Cincinnati Children's win rare honor". Cincinnati Business Courier. Retrieved May 14, 2020.
  17. ↑ "ASBMB Today" (PDF). Retrieved May 13, 2020.
  18. ↑ "NIH establishes working group on the future biomedical research workforce". National Institutes of Health (NIH). August 1, 2015. Retrieved May 14, 2020.
  19. ↑ "National Academy of Inventors Inaugural Annual Conference" (PDF). Retrieved May 13, 2020.
  20. ↑ Mentoring Achievement Award: Sandra Degen, PhD , retrieved May 14, 2020
  21. 1 2 3 4 5 6 7 8 9 10 11 12 13 "Sandra J. Degen - Publications". academictree.org. Retrieved May 14, 2020.
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