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Janette Mcallister

TitleProfessor
InstitutionCollege of Medicine
DepartmentPathology
Address500 University Drive Hershey PA 17033
Mailbox: H083
Phone7175313588

 Overview 
 overview
PREFERRED TITLE/ROLE:

Professor of Pathology, Obstetrics and Gynecology, and Cellular and Molecular Physiology

GRADUATE PROGRAM AFFILIATIONS:

Cell and molecular Biology, Integrative Biosciences, MD/PhD Degree Program, Physiology

EDUCATION:

Ph.D., University of California, San Diego, 1987
Postdoctoral Training, University of Texas Southwestern Medical Center, Dallas, 1987-1991

NARRATIVE:

The cellular mechanisms underlying excess ovarian androgen production in patients with polycystic ovary syndrome (PCOS) are unknown. The central research emphasis of my laboratory involves the examination of the intrinsic defects in steroidogenic enzyme expression that result in increased androgen production in patients with insulin resistance and PCOS. For a number of years, it has been proposed that excessive androgen production in PCOS results from intrinsic abnormalities in steroid production by ovarian theca interna cells. During the past 6 years, my primary interest has been to develop long-term functional culture systems for normal and PCOS theca interna and granulosa cells which can be grown and propagated for successive population doublings with maintenance of inducible steroidogenic capacity. Using these conditions, we have established for the first time, that increased androgen production is a stable phenotype of PCOS theca cells that not only results from preferentially increased 17a-hydroxylase (CYP17) expression, but involves the upregulation of other steroidogenic enzymes including cholesterol side-chain cleavage (CYP11A), and 3b-hydroxysteroid dehydrogenase (3b-HSDII). We have also obtained the first data to show that the mitogen activated protein kinase signaling pathway (MAPK) is aberrant in PCOS granulosa and theca cells. My laboratory is currently in the process of examining the relative contributions of transcriptional and post-transcriptional regulation to CYP17, CYP11A, and 3b-HSDII gene expression in normal and PCOS theca cells. We are in the process of characterizing the specific components of the MAPK pathway that are altered in PCOS theca and granulosa cells. We are also in the process of utilizing microarray analysis, serial analysis of gene expression (SAGE) and suppressive subtractive hybridization (SSH), to characterize the complete repertoire of differentially transcribed genes, the common transcription factor mediators, and additional signal transduction cascade(s) that are abnormal in PCOS granulosa and theca cells. As a consequence of these ongoing studies, we believe that critical information regarding the cellular basis for increased androgen production in the PCOS ovary will be obtained, which will be applicable to other clinical manifestations of PCOS, such as follicular growth arrest, infertility, endometrial hyperplasia/cancer, obesity, and insulin resistance.


 Bibliographic 
 selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. McAllister JM, Modi B, Miller BA, Biegler J, Bruggeman R, Legro RS, Strauss JF. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci U S A. 2014 Apr 15; 111(15):E1519-27.
    View in: PubMed
  2. Wickenheisser JK, Biegler JM, Nelson-Degrave VL, Legro RS, Strauss JF, McAllister JM. Cholesterol side-chain cleavage gene expression in theca cells: augmented transcriptional regulation and mRNA stability in polycystic ovary syndrome. PLoS One. 2012; 7(11):e48963.
    View in: PubMed
  3. Strauss JF, McAllister JM, Urbanek M. Persistence pays off for PCOS gene prospectors. J Clin Endocrinol Metab. 2012 Jul; 97(7):2286-8.
    View in: PubMed
  4. Ewens KG, Stewart DR, Ankener W, Urbanek M, McAllister JM, Chen C, Baig KM, Parker SC, Margulies EH, Legro RS, Dunaif A, Strauss JF, Spielman RS. Family-based analysis of candidate genes for polycystic ovary syndrome. J Clin Endocrinol Metab. 2010 May; 95(5):2306-15.
    View in: PubMed
  5. Chen C, Wickenheisser J, Ewens KG, Ankener W, Legro RS, Dunaif A, McAllister JM, Spielman RS, Strauss JF. PDE8A genetic variation, polycystic ovary syndrome and androgen levels in women. Mol Hum Reprod. 2009 Aug; 15(8):459-69.
    View in: PubMed
  6. Legro RS, McAllister JM. Heirarchical clustering and beyond in PCOS endometrium: brave new world. J Clin Endocrinol Metab. 2009 Apr; 94(4):1084-5.
    View in: PubMed
  7. Huang AM, Rudelius M, Sharan S, McAllister JM, Raffeld M, Christenson LK, Sterneck E. The Cebpd (C/EBPdelta) gene is induced by luteinizing hormones in ovarian theca and interstitial cells but is not essential for mouse ovary function. PLoS One. 2007; 2(12):e1334.
    View in: PubMed
  8. Wickenheisser JK, Nelson-DeGrave VL, McAllister JM. Human ovarian theca cells in culture. Trends Endocrinol Metab. 2006 Mar; 17(2):65-71.
    View in: PubMed
  9. Ho CK, Wood JR, Stewart DR, Ewens K, Ankener W, Wickenheisser J, Nelson-Degrave V, Zhang Z, Legro RS, Dunaif A, McAllister JM, Spielman R, Strauss JF. Increased transcription and increased messenger ribonucleic acid (mRNA) stability contribute to increased GATA6 mRNA abundance in polycystic ovary syndrome theca cells. J Clin Endocrinol Metab. 2005 Dec; 90(12):6596-602.
    View in: PubMed
  10. Wickenheisser JK, Nelson-DeGrave VL, Hendricks KL, Legro RS, Strauss JF, McAllister JM. Retinoids and retinol differentially regulate steroid biosynthesis in ovarian theca cells isolated from normal cycling women and women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Aug; 90(8):4858-65.
    View in: PubMed
  11. Wickenheisser JK, Nelson-Degrave VL, McAllister JM. Dysregulation of cytochrome P450 17alpha-hydroxylase messenger ribonucleic acid stability in theca cells isolated from women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2005 Mar; 90(3):1720-7.
    View in: PubMed
  12. Wood JR, Nelson-Degrave VL, Jansen E, McAllister JM, Mosselman S, Strauss JF. Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects. Physiol Genomics. 2005 Feb 10; 20(3):233-43.
    View in: PubMed
  13. Nelson-Degrave VL, Wickenheisser JK, Hendricks KL, Asano T, Fujishiro M, Legro RS, Kimball SR, Strauss JF, McAllister JM. Alterations in mitogen-activated protein kinase kinase and extracellular regulated kinase signaling in theca cells contribute to excessive androgen production in polycystic ovary syndrome. Mol Endocrinol. 2005 Feb; 19(2):379-90.
    View in: PubMed
  14. Wood JR, Ho CK, Nelson-Degrave VL, McAllister JM, Strauss JF. The molecular signature of polycystic ovary syndrome (PCOS) theca cells defined by gene expression profiling. J Reprod Immunol. 2004 Aug; 63(1):51-60.
    View in: PubMed
  15. Wickenheisser JK, Nelson-DeGrave VL, Quinn PG, McAllister JM. Increased cytochrome P450 17alpha-hydroxylase promoter function in theca cells isolated from patients with polycystic ovary syndrome involves nuclear factor-1. Mol Endocrinol. 2004 Mar; 18(3):588-605.
    View in: PubMed
  16. Nelson-DeGrave VL, Wickenheisser JK, Cockrell JE, Wood JR, Legro RS, Strauss JF, McAllister JM. Valproate potentiates androgen biosynthesis in human ovarian theca cells. Endocrinology. 2004 Feb; 145(2):799-808.
    View in: PubMed
  17. Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, Clawson G. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol. 2003 Jun; 120(6):905-14.
    View in: PubMed
  18. Wood JR, Nelson VL, Ho C, Jansen E, Wang CY, Urbanek M, McAllister JM, Mosselman S, Strauss JF. The molecular phenotype of polycystic ovary syndrome (PCOS) theca cells and new candidate PCOS genes defined by microarray analysis. J Biol Chem. 2003 Jul 18; 278(29):26380-90.
    View in: PubMed
  19. Jabara S, Christenson LK, Wang CY, McAllister JM, Javitt NB, Dunaif A, Strauss JF. Stromal cells of the human postmenopausal ovary display a distinctive biochemical and molecular phenotype. J Clin Endocrinol Metab. 2003 Jan; 88(1):484-92.
    View in: PubMed
  20. Yamamoto N, Christenson LK, McAllister JM, Strauss JF. Growth differentiation factor-9 inhibits 3'5'-adenosine monophosphate-stimulated steroidogenesis in human granulosa and theca cells. J Clin Endocrinol Metab. 2002 Jun; 87(6):2849-56.
    View in: PubMed
  21. Strauss JF, Wood JR, Christenson LK, McAllister JM. Strategies to elucidate the mechanism of excessive theca cell androgen production in PCOS. Mol Cell Endocrinol. 2002 Jan 25; 186(2):183-8.
    View in: PubMed
  22. Nelson VL, Qin KN, Rosenfield RL, Wood JR, Penning TM, Legro RS, Strauss JF, McAllister JM. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2001 Dec; 86(12):5925-33.
    View in: PubMed
  23. Christenson LK, Osborne TF, McAllister JM, Strauss JF. Conditional response of the human steroidogenic acute regulatory protein gene promoter to sterol regulatory element binding protein-1a. Endocrinology. 2001 Jan; 142(1):28-36.
    View in: PubMed
  24. Wickenheisser JK, Quinn PG, Nelson VL, Legro RS, Strauss JF, McAllister JM. Differential activity of the cytochrome P450 17alpha-hydroxylase and steroidogenic acute regulatory protein gene promoters in normal and polycystic ovary syndrome theca cells. J Clin Endocrinol Metab. 2000 Jun; 85(6):2304-11.
    View in: PubMed
  25. Devoto L, Christenson LK, McAllister JM, Makrigiannakis A, Strauss JF. Insulin and insulin-like growth factor-I and -II modulate human granulosa-lutein cell steroidogenesis: enhancement of steroidogenic acute regulatory protein (StAR) expression. Mol Hum Reprod. 1999 Nov; 5(11):1003-10.
    View in: PubMed
  26. Christenson LK, Johnson PF, McAllister JM, Strauss JF. CCAAT/enhancer-binding proteins regulate expression of the human steroidogenic acute regulatory protein (StAR) gene. J Biol Chem. 1999 Sep 10; 274(37):26591-8.
    View in: PubMed
  27. Nelson VL, Legro RS, Strauss JF, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries. Mol Endocrinol. 1999 Jun; 13(6):946-57.
    View in: PubMed
  28. Christenson LK, McAllister JM, Martin KO, Javitt NB, Osborne TF, Strauss JF. Oxysterol regulation of steroidogenic acute regulatory protein gene expression. Structural specificity and transcriptional and posttranscriptional actions. J Biol Chem. 1998 Nov 13; 273(46):30729-35.
    View in: PubMed
  29. Ogo A, Waterman MR, McAllister JM, Kagawa N. The homeodomain protein Pbx1 is involved in cAMP-dependent transcription of human CYP17. Arch Biochem Biophys. 1997 Dec 1; 348(1):226-31.
    View in: PubMed
  30. Sugawara T, Kiriakidou M, McAllister JM, Kallen CB, Strauss JF. Multiple steroidogenic factor 1 binding elements in the human steroidogenic acute regulatory protein gene 5'-flanking region are required for maximal promoter activity and cyclic AMP responsiveness. Biochemistry. 1997 Jun 10; 36(23):7249-55.
    View in: PubMed
  31. Sugawara T, Kiriakidou M, McAllister JM, Holt JA, Arakane F, Strauss JF. Regulation of expression of the steroidogenic acute regulatory protein (StAR) gene: a central role for steroidogenic factor 1. Steroids. 1997 Jan; 62(1):5-9.
    View in: PubMed
  32. Kiriakidou M, McAllister JM, Sugawara T, Strauss JF. Expression of steroidogenic acute regulatory protein (StAR) in the human ovary. J Clin Endocrinol Metab. 1996 Nov; 81(11):4122-8.
    View in: PubMed
  33. Helm KF, McAllister JM, Helm F. Radiation keratosis associated with exposure to a gold ring. Cutis. 1996 Jun; 57(6):435-6.
    View in: PubMed
  34. McAllister JM. Functional, long-term human theca and granulosa cell cultures from polycystic ovaries. Endocrine. 1995 Feb; 3(2):143-9.
    View in: PubMed
  35. McAllister JM, Byrd W, Simpson ER. The effects of growth factors and phorbol esters on steroid biosynthesis in isolated human theca interna and granulosa-lutein cells in long term culture. J Clin Endocrinol Metab. 1994 Jul; 79(1):106-12.
    View in: PubMed
  36. Hornsby PJ, McAllister JM. Culturing steroidogenic cells. Methods Enzymol. 1991; 206:371-80.
    View in: PubMed
  37. McAllister JM, Mason JI, Byrd W, Trant JM, Waterman MR, Simpson ER. Proliferating human granulosa-lutein cells in long term monolayer culture: expression of aromatase, cholesterol side-chain cleavage, and 3 beta-hydroxysteroid dehydrogenase. J Clin Endocrinol Metab. 1990 Jul; 71(1):26-33.
    View in: PubMed
  38. McAllister JM, Kerin JF, Trant JM, Estabrook RW, Mason JI, Waterman MR, Simpson ER. Regulation of cholesterol side-chain cleavage and 17 alpha-hydroxylase/lyase activities in proliferating human theca interna cells in long term monolayer culture. Endocrinology. 1989 Oct; 125(4):1959-66.
    View in: PubMed
  39. McAllister JM, Hornsby PJ. TPA inhibits the synthesis of androgens and cortisol and enhances the synthesis non-17 alpha-hydroxylated steroids in cultured human adrenocortical cells. Endocrinology. 1987 Nov; 121(5):1908-10.
    View in: PubMed
  40. Hornsby PJ, Hancock JP, Vo TP, Nason LM, Ryan RF, McAllister JM. Loss of expression of a differentiated function gene, steroid 17 alpha-hydroxylase, as adrenocortical cells senescence in culture. Proc Natl Acad Sci U S A. 1987 Mar; 84(6):1580-4.
    View in: PubMed
  41. Meidan R, Lim P, McAllister JM, Hsueh AJ. Hormonal regulation of androgen biosynthesis by primary cultures of testis cells from neonatal rats. Endocrinology. 1985 Jun; 116(6):2473-82.
    View in: PubMed
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