William J. Hendry PhD

1. With the research group I joined for my PhD degree (Mentor – Dr. Wendell W. Leavitt; Worcester Foundation for Experimental Biology), I participated in some of their analyses of steroid hormone/receptor regulation in the hamster uterus. However, the real focus of my thesis project was development and characterization of a unique experimental hamster model for the human “DES syndrome”. Indeed, it was that medical misadventure that established diethylstilbestrol (DES) as a transplacental carcinogen and the prototypical endocrine disruptor agent.

2. My initial post-doctoral position (Mentor – Dr. Benjamin J. Danzo; Vanderbilt University School of Medicine) was with a group that studied the structure and regulated function of estrogen receptors in male reproductive tract organs. My project with that group involved analyses of the function and modification of estrogen receptors by a protease active in the epididymis of mature but not immature rabbits; a process that may be responsible for decreased estrogen sensitivity in the adult epididymis.

3. With my next mentor and collaborator (Dr. Robert W. Harrison III; Vanderbilt University School of Medicine and University of Arkansas for Medical Sciences), I investigated the biochemistry and molecular biology of glucocorticoid receptors. In particular, my project focused on the dynamics of glucocorticoid receptor protein levels and the effects of such dynamics on specific glucocorticoid-dependent responses. Those studies greatly expanded my molecular manipulation and analytical skills plus they required me to master new in vitro (cell culture) techniques.

4. While at WSU, my continued engagement with the topics of endocrine disruption in general and the DES Syndrome in particular included further definition of the progression and molecular aspects of that phenomenon in both the female and male hamster reproductive tract. Recently, we expanded our investigation of the phenomenon to the epigenetic level. More specifically, we initiated studies of altered miRNA expression in our experimental system and they again involved both undergraduate and graduate students. It is also important to note that such activities are very relevant to the paradigm now recognized by NIH as the Fetal Basis of Adult Disease or FeBAD.

5. Importantly and as introduced in the Personal Statement section above, key findings about the basic mechanisms of neonatal DES-induced disruption of the female reproductive tract relied on my ability to develop and teach other scientists and students the very effective and compliant hamster cheek pouch transplantation protocol. More specifically, use of that protocol allowed us to prove that neonatal DES exposure directly and permanently disrupts the developing hamster uterus (initiating event) so that it responds abnormally later in life to stimulation promoting event) with the natural ovarian steroid, estradiol. We are now generating Proof-Of-Principle results that support further testing of the cheek pouch as a xenotransplantation site and as the basis of a patient “avatar” system for human ovarian cancer and, most recently, human head and neck squamous cell cancer.

While serving as Department Chair, I continue to teach at both the undergraduate and graduate levels (BIOL 527, Comparative Vertebrate Anatomy [lecture and lab]; BIOL 534/535, Human Physiology [lecture and lab]; and BIOL 730, Cancer Biology [lecture]) and maintain an independent research agenda. That agenda involves cellular and molecular studies using both in vitro and in vivo approaches. More specifically, I developed a unique animal experimental system to study: 1) the topic of endocrine disruption in general and 2) a medical misadventure known as the “DES Syndrome” in particular. It is important to note that key findings about the fundamental mechanisms of neonatal DES-induced endocrine disruption in our system depended on my success in developing a hamster cheek pouch transplantation protocol and passing on that protocol to other investigators, graduate students, and even undergraduate students. Also, through my participation with the K-INBRE, WMREF, and KUMC-W entities defined above and below, I am directly involved with the now expanding partnership between WSU and the local biomedical community; a partnership that includes a growing cohort of Translational Research projects.

1. With the research group I joined for my PhD degree (Mentor – Dr. Wendell W. Leavitt; Worcester Foundation for Experimental Biology), I participated in some of their analyses of steroid hormone/receptor regulation in the hamster uterus. However, the real focus of my thesis project was development and characterization of a unique experimental hamster model for the human “DES syndrome”. Indeed, it was that medical misadventure that established diethylstilbestrol (DES) as a transplacental carcinogen and the prototypical endocrine disruptor agent.
a. Evans RW, Chen TJ, Hendry WJ, 3rd, Leavitt WW. Progesterone regulation of estrogen receptor in the hamster uterus during the estrous cycle. Endocrinology. 1980;107:383-90. PMID: 7190093
b. Leavitt WW, Evans RW, Hendry WJ, 3rd. Etiology of DES-induced uterine tumors in the Syrian hamster. Adv Exp Med Biol. 1982;138:63-86. PMID: 7342722
c. Hendry WJ, 3rd, Leavitt WW. Binding and retention of estrogen in the uterus of hamsters treated neonatally with diethylstilbestrol. J Steroid Biochem. 1982;17:479-87. PMID: 7176641
d. Hendry WJ, 3rd, Leavitt WW. Altered morphogenesis of the immature hamster uterus following neonatal exposure to diethylstilbestrol. Differentiation. 1993;52:221-7. PMID: 8482438
2. My initial post-doctoral position (Mentor – Dr. Benjamin J. Danzo; Vanderbilt University School of Medicine) was with a group that studied the structure and regulated function of estrogen receptors in male reproductive tract organs. My project with that group involved analyses of the function and modification of estrogen receptors by a protease active in the epididymis of mature but not immature rabbits; a process that may be responsible for decreased estrogen sensitivity in the adult epididymis.
a. Danzo BJ, Eller BC, Hendry WJ, 3rd. Identification of cytoplasmic estrogen receptors in the accessory sex organs of the rabbit and their comparison to the cytoplasmic estrogen receptor in the epididymis. Mol Cell Endocrinol. 1983;33:197-209. PMID: 6653871
b. Hendry WJ, 3rd, Eller BC, Orgebin-Crist MC, Danzo BJ. Hormonal effects on the estrogen receptor system in the epididymis and accessory sex organs of sexually immature rabbits. J Steroid Biochem. 1985;23:39-49. PMID: 4021492
c. Hendry WJ, 3rd, Danzo BJ. Structural conversion of cytosolic steroid receptors by an age-dependent epididymal protease. J Steroid Biochem. 1985;23:883-93. PMID: 3912613
d. Hendry, WJ, 3rd, Danzo BJ. Further characterization of a steroid receptor-active protease from the mature rabbit epididymis. J Steroid Biochem. 1986;25:433-43. PMID: 3534465
3. With my next mentor and collaborator (Dr. Robert W. Harrison III; Vanderbilt University School of Medicine and University of Arkansas for Medical Sciences), I investigated the biochemistry and molecular biology of glucocorticoid receptors. In particular, my project focused on the dynamics of glucocorticoid receptor protein levels and the effects of such dynamics on specific glucocorticoid-dependent responses. Those studies greatly expanded my molecular manipulation and analytical skills plus they required me to master new in vitro (cell culture) techniques.
a. Hendry WJ, 3rd, Danzo BJ, Harrison RW, 3rd. Analysis of the disruptive action of an epididymal protease and the stabilizing influence of molybdate on nondenatured and denatured glucocorticoid receptor. Endocrinology. 1987;120:629-39. PMID: 3542507
b. Harrison RW, 3rd, Lippman SS, Hendry WJ, 3rd, Chien MC. Isolation of a genomic sublibrary enriched for glucocorticoid-regulated genes. DNA Cell Biol. 1990;9:95-102. PMID: 2344394
c. Hendry WJ, 3rd, Hakkak R, Cornett LE. Selective loss of glucocorticoid-dependent responses in a variant of the DDT1MF-2 tumor cell line. Cancer Res. 1992;52:2516-22. PMID: 1314696
d. Hendry WJ, 3rd, Hakkak R, Harrison RW, 3rd. An analysis of autologous glucocorticoid receptor protein regulation in AtT-20 cells also reveals differential specificity of the BuGR2 monoclonal antibody. Biochim Biophys Acta. 1993;1178:176-88. PMID: 8347676
4. While at WSU, my continued engagement with the topics of endocrine disruption in general and the DES Syndrome in particular included further definition of the progression and molecular aspects of that phenomenon in both the female and male hamster reproductive tract. Recently, we expanded our investigation of the phenomenon to the epigenetic level. More specifically, we initiated studies of altered miRNA expression in our experimental system and they again involved both undergraduate and graduate students. It is also important to note that such activities are very relevant to the paradigm now recognized by NIH as the Fetal Basis of Adult Disease or FeBAD.
a. Zheng X, Hendry WJ, 3rd. Neonatal diethylstilbestrol treatment alters the estrogen-regulated expression of both cell proliferation and apoptosis-related proto-oncogenes (c-jun, c-fos, c-myc, bax, bcl-2, and bcl-x) in the hamster uterus. Cell Growth Differ. 1997;8:425-34. PMID: 9101088
b. Hendry WJ, 3rd, DeBrot BL, Zheng X, Branham WS, Sheehan DM. Differential activity of diethylstilbestrol versus estradiol as neonatal endocrine disruptors in the female hamster (Mesocricetus auratus) reproductive tract. Biol Reprod. 1999;61:91-100. PMID: 10377036
c. Hendry WJ, Hariri HY, Alwis ID, Gunewardena SS, Hendry IR. Altered Gene Expression Patterns During the Initiation and Promotion Stages of Neonatally Diethylstilbestrol-Induced Hyperplasia/Dysplasia/Neoplasia in the Hamster Uterus. Reprod Toxicol. 2014;50:68-56. PMCID: PMC4261067
d. Hendry WJ III, Weaver BP, Naccarato TR, Khan SA. Differential progression of neonatal diethylstilbestrol-induced disruption of the hamster (Mesocricetus auratus) testis and seminal vesicle. Reprod Toxicol 2006;21:225-240. PMID: 16439099
e. Padmanabhan R, Hendry IR, Knapp JR, Shuai, B Hendry, WJ. Altered microRNA expression patterns during the initiation and promotion stages of neonatal diethylstilbestrol-induced dysplasia/neoplasia in the hamster (Mesocricetus auratus) uterus. (2017) Cell Biol Toxicol 2017 Mar 6. doi: 10.1007/s10565-017-9389-6. [Epub ahead of print]
5. Importantly and as introduced in the Personal Statement section above, key findings about the basic mechanisms of neonatal DES-induced disruption of the female reproductive tract relied on my ability to develop and teach other scientists and students the very effective and compliant hamster cheek pouch transplantation protocol. More specifically, use of that protocol allowed us to prove that neonatal DES exposure directly and permanently disrupts the developing hamster uterus (initiating event) so that it responds abnormally later in life to stimulation promoting event) with the natural ovarian steroid, estradiol. We are now generating Proof-Of-Principle results that support further testing of the cheek pouch as a xenotransplantation site and as the basis of a patient “avatar” system for human ovarian cancer and, most recently, human head and neck squamous cell cancer.
a. Hendry WJ, 3rd, Branham WS, Sheehan DM. The hamster cheek pouch as a convenient ectopic site for studies of uterine morphogenesis and endocrine responsiveness. Differentiation. 1992;51:49-54. PMID: 1451961
b. Hendry WJ, 3rd, Zheng X, Leavitt WW, Branham WS, Sheehan DM. Endometrial hyperplasia and apoptosis following neonatal diethylstilbestrol exposure and subsequent estrogen stimulation in both host and transplanted hamster uteri. Cancer Res. 1997;57:1903-8. PMID: 9157983
c. Hendry WJ, 3rd, Sheehan DM, Khan SA, May JV. Developing a laboratory animal model for perinatal endocrine disruption: The hamster chronicles. Exp Biol Med. 2002;227:709-23. PMID: 12324652
d. Alwis ID, Maroni DM, Hendry IR, Roy SK, May JV, Leavitt WW, et al. Neonatal diethylstilbestrol exposure disrupts female reproductive tract structure/function via both direct and indirect mechanisms in the hamster. Reprod Toxicol. 2011;32:472-83. PMCID: PMC3225713

1975-1977 -Junior Instructor, University College, Northeastern University, Boston, MA.
1978 -Instructor, University College, Northeastern University, Boston, MA.
1982-1984 -Research Associate (mentor – Dr. Benjamin J. Danzo), Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN.
1984-1985 -Research Instructor (mentor – Dr. Robert W. Harrison III), Division of Endocrinology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
1985-1991 -Assistant Professor of Medicine and Adjunct Assistant Professor of Biochemistry, Division of Endocrinology, Dept. of Med., University of Arkansas for Medical Sciences, Little Rock, AR.
1992-1999 -Associate Professor, Department of Biological Sciences, Wichita State University, Wichita, KS.
1992-2006 -Graduate Coordinator, Department of Biological Sciences, Wichita State University, Wichita, KS.
1996-2001 -Scientist, The Women’s Research Institute and University of Kansas School of Medicine-Wichita, Department of Obstetrics and Gynecology, Wichita, KS.
1997-1998 -Director, Cell Culture Core Facility, Dept. of Biol. Sciences, Wichita State University, Wichita, KS.
1999- -Director, Cell Imaging Core Facility, Department of Biological Sciences, Wichita State University, Wichita, KS.
1998 -Interim Chairperson, Department of Biological Sciences, Wichita State University, Wichita, KS.
1999- -Full Professor, Department of Biological Sciences, Wichita State University, Wichita, KS.
2006- -Chairperson, Department of Biological Sciences, Wichita State University, Wichita, KS.
2006- -Director, Animal Care Facility, Dept. of Biological Sciences, Wichita State University, Wichita, KS.
2011- -Adjunct Professor, Department of Medical Sciences, University of Kansas School of Medicine-Wichita (KUMC-W), KS.

-Member of the American Association for the Advancement of Science; Society for the Study of Reproduction, American Society of Biological Chemists; The Endocrine Society; Society for Experimental Biology and Medicine; American Association for Cancer Research
1990 -Ad Hoc reviewer for the Cellular Biosciences-Physiological Processes Unit of NSF
1990-1996 -Editorial Board for the Proceedings of the Society for Experimental Biology and Medicine
1997 -Ad Hoc reviewer for the Animal Biology Program at NSF
1998 -State reviewer for the U.S. Environmental Protection Agency / Kansas EPSCoR Program
1999-2000 -Reviewer of proposals submitted to the NSF-Kansas EPSCoR program (as member of the K*STAR [Kansas Science and Technology Advanced Research] Faculty Advisory Committee)
2001- -Wichita Coordinator and member of the Network Steering Committee for the Kansas IDeA Network of Biomedical Research Excellence (K-INBRE) funded by NIH.
2002-2003 -Invited grant reviewer for the Lalor Foundation, Inc., Boston, MA
2002-2005 -Member; Internal Advisory Committee for the National Institutes of Health (NIH) Centers of Biomedical Research Excellence (COBRE) grant application process from the state of Kansas
2002- -Member of the Board of Directors (and President, 2009-13 ) for the Wichita Medical Research and Education Foundation (WMREF), Wichita KS
2002- -Member of the Board of Trustees for the H.L. Snyder Medical Research Foundation, Winfield KS
2005 -Full Professor Incentive Award, Wichita State University, Wichita, KS.
2007 -Member of ICER Study Section for the National Institutes of Health
2009 -Member of the Cellular, Molecular and Integrative Reproduction [CMIR] Study Section for NIH
2009- -Member of the Internal Advisory Committee for the NIH-funded Program Project (P01AG029531; The Aging Pituitary-Gonadal Axis) at the Department of Biological Sciences, Wichita State University, Wichita, KS.
2016- -Affiliate member of the NCI-Designated University of Kansas Cancer Center

Education