The Faculty in Reproductive Biology at Illinois

Paul S. Cooke

Veterinary Biosciences
Ph.D., University of California, Berkeley

To e-mail Dr. Cooke use: p-cooke@uiuc.edu

Current and Future Research Focus

The research interests of the lab involve two major areas, 1) reproductive biology and 2) adipogenesis and obesity.

Reproductive Biology

The lab has a major interest in both male and female reproductive biology. Dr. Cooke is  a member of the UIUC Reproductive Training Program. One long-term focus is how the number of Sertoli cells, the supporting cells in the seminiferous epithelium of the testis that regulate spermatogenesis, are established during development. The number of Sertoli cells regulates the magnitude of spermatogenesis, so the factors regulating Sertoli cell number are the primary determinant of the ultimate magnitude of sperm production.
A new area of focus in the lab is the role of the Sertoli cell transcription factor ERM on stem cell spermatogonia in the testis. In conjunction with Dr. Rex Hess at Illinois and Ken Murphy at Washington University School of Medicine, we are using an ERM knockout (in which the ERM gene has been disabled) to understand how ERM functions in the Sertoli cell and indirectly in the spermatogonia to maintain the stem cells responsible for sperm production.
The lab also has interests in both male and female reproductive toxicology, specifically   in the roles of aryl hydrocarbons such as dioxins, environmental estrogens and phthalates in reproductive development and function. Dr. Cooke is a member of the UIUC Reproductive Toxicology Training Program. Finally, a current project with Dr. David Sherwood at Illinois to address the relative roles of stromal and epithelial receptors for relaxin in mediating the effects of this hormone in the female reproductive tract continues our long-standing interests in stromal-epithelial interactions in regulating hormonal responsiveness in the female reproductive tract.

Adipogenesis and Obesity

The major questions we are addressing in the area of adipose biology are the molecular mechanisms of how the number of adipocytes are normally established in a person or animal, and what role adipocyte number has in obesity. We and others have shown that estrogens are major regulators of adipose tissue in both males and females, and these compounds can produce alterations in both adipocyte number and/or size. Our current research in this area involves experiments to determine the mechanisms of how estrogens (both endogenous and environmental estrogens such as the soy phytoestrogen genistein) effect the development of adipose tissue, and specifically how they regulate the establishment of adipocyte number and what the long term consequences of alterations in adipocyte number are.

Selected Publications:

Cooke PS, Buchanan DL, Young P, Setiawan T, Brody J, Korach KS, Taylor J, Lubahn DB, Cunha GR. (1997) Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium. Proc Natl Acad Sci U S A. 94:6535-40.

Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS. (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci U S A. 97:12729-34.

Yellayi S, Naaz A, Szewczykowski MA, Sato T, Woods JA, Chang J, Segre M, Allred CD, Helferich WG, Cooke PS. (2002) The phytoestrogen genistein induces thymic and immune changes: a human health concern? Proc Natl Acad Sci U S A. 99:7616-21.

Cooke PS, Hess RA, Simon L, Schlesser HN, Carnes K, Tyagi G, Hofmann M-C, Murphy KM (2006) The transcription factor Ets-Related Molecule (ERM) is essential for stem cell maintenance and self-renewal. Animal Reproduction 3:98-107.

Cooke PS, Selvaraj V, Yellayi S (2006) Genistein, estrogen receptors and the acquired immune response. Journal of Nutrition 136:704-708.

Hess RA, Cooke PS, Hofmann M-C, Murphy KM (2006) Mechanistic insights into the regulation of the spermatogonial stem cell niche. Cell Cycle 5:e1-e7.

Sridharan S, Simon L, Meling DD, Cyr DG, Gutstein DE, Fishman GI, Guillou F, Cooke PS (2007) Proliferation of adult Sertoli cells following conditional knock out of the gap junctional protein GJA1 (Connexin 43) Biology of Reproduction 76:804-812.

Cooke PS, Holsberger D, Cimafranca M, Meling D, Beals C, Nakayama K, Nakayama K, Kiyokawa H (2007) The F box protein Skp2 regulates adipose mass and adipocyte number in vivo. Obesity 15:1400-1408.

Jansen HT, Kirby JD, Cooke PS, Arambepola N, Iwamoto GA (2007) Endocrine, anatomical, and behavioral abnormalities associated with transient neonatal hypothyroidism in the golden hamster (Mesocricetus auratus): Evidence supporting a role for thyroid hormones in the normal development of the male reproductive axis. Physiology and Behavior 90:771-781.

Goyal HO, Braden TD, Cooke PS, Szewczykowski MA, Williams CS, Dalvi P, Williams JW, Newbold RR, Herbert RA (2007) Estrogen receptor-a mediates estrogen-inducible abnormalities in the developing penis. Reproduction 133:1057-1067.

Simon L, Ekman GC, Tyagi G, Hess RA, Murphy KM, Cooke PS (2007) Common and distinct factors regulate expression of ERM and GDNF, Sertoli cell proteins essential for spermatogonial stem cell maintenance. Experimental Cell Research 313:3090-3099.

Schlesser HN, Simon L, Hofmann MC, Murphy KM, Hess RA, Cooke PS Effects of ets variant gene 5 (ERM) on testis and body growth, time course of spermatogonial stem cell loss and fertility in mice. Biology of Reproduction (in press)

Morrow CMK, Hostetler CE, Griswold MD, Hofmann M-C, Murphy KM, Cooke PS, Hess RA ETV5 is required for continuous spermatogenesis in adult mice and may mediate blood-testes barrier function and testicular immune privilege. Ann NY Acad Sci (in press)

Sridharan S, Brehm R, Bergmann M, Cooke PS, Role of connexin 43 in Sertoli cells of testis. Ann NY Acad Sci (in press)

View Publications by Paul S. Cooke listed on the National Library of Medicine (PubMed)

Last updated August 12, 2003

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