Areas of Interest
We study gene regulation by steroid hormones, focusing on transcriptional mechanisms, hormone-dependent cancers, and sex-biased gene action. Steroid receptors are ligand-activated transcription factors with diverse functions, yet several act via a common DNA binding site and use common coregulators. We examine how specific regulation is attained by the androgen receptor (AR).
To study the central role of AR in prostate cancer and to model human disease, we converted the mouse gene to the human sequence (humanized AR mice). Variant hAR alleles in mice confer differences in cancer initiation, progression, and response to therapy. This allowed us to study treatment resistance, particularly by somatic AR mutations. In both mouse and human tumors, AR variants use diverse mechanisms to evade therapy. In collaborative studies, variant ARs also impact brain development and behaviors.
Sex differences in gene expression broadly impact physiology and incidence of many diseases. We identified in mutant mice a KRAB zinc finger repressor (Regulator-of-sex-limitation) that influences sex-biased expression in liver of genes acting in lipid and steroid metabolism. Rsl deficiency leads to early puberty, lack of dietary stress response and susceptibility to obesity and diabetes. Rsl provides insight into KRAB-ZFP epigenetic mechanisms as well as evolution of this recently expanded gene family.
Honors & Awards
- 2020 Teacher’s Teacher Award, from the Michigan Medicine Academy of Medical Educators2015 Ingbar Award for Distinguished Service, Endocrine Society
- 2015 Michigan Society of Fellows, Senior Member
- 2014 Gorski Lectureship in Biochemistry, Great Lakes Nuclear Receptor Conference
- 2014 SWIU/SBUR Award for Excellence in Urological Research
- 2013 AAAS Fellow
- 2013 Chair of the Endocrine Society Annual Symposium
- 2013-16 Elected Basic Science Representative to Endocrine Society Council
- 2012 Inaugural Member, League of Educational Excellence, U of M
- 2010 Basic Science Chair of the Endocrine Society Annual Symposium
- 2007-09 Member, Board of Scientific Counselors of the NIH National Toxicology Program
- 2007 Crosby Award, NSF ADVANCE at the University of Michigan
- 2006-09 Chair, UICC Review Panel for ACS Fellowships
- 2005- Advisor, NIEHS Center for Rodent Genetics
- 1999-2003 Member, American Cancer Society Council
- 1996 Career Development Award, Michigan Agenda for Women
- 1978 Kallman Award
1982 Columbia University, Post-doc (Jane Coffin Childs Postdoc Fellowship)
1978 Stanford University, Ph.D. (National Science Foundation Grad Fellowship)
1973 Yale University, B.S.
Kregel S, Bagamasbad P, He S, LaPensee E, Raji Y, Brogley M, Chinnaiyan A, Cieslik M, Robins DM: (2020) Differential modulation of the androgen receptor for prostate cancer therapy depends on the DNA response element. Nucleic Acids Research 48: 4741-4755.
He Y, Mi J, Olson A, Aldal J, Hoker E, Yu E, Lee D, Kim W, Robins DM, Geradts J, Sun Z: (2020) Androgen receptor with short polyglutamine tract preferably enhances Wnt/b-catenin-mediated prostate tumorigenesis. Oncogene 39: 3276-91.
Nath S, Yu Z, Gipson T, Marsh G, Yoshidome E, Robins D, Todi S, Housman D, Lieberman A: (2018) Androgen receptor polyglutamine expansion drives age-dependent quality control defects and muscle dysfunction. J Clin Invest 128:3630-41
Higgins J, Brogley M, Palanisamy N, Mehra R, Ittmann M, Li J, Tomlins S, Robins DM: (2015) Interaction of AR, ETV1, and PTEN pathways in mouse prostate varies with pathological stage and predicts cancer progression. Hormones & Cancer 6: 67-86.
Ellegood J, Anagnostou E, Babineau B, Crawley J et al: (2015) Clustering autism: using neuroanatomical differences in 26 mouse models to gain insight into heterogeneity. Molecular Psychiatry 20: 118-25.
Krebs CJ, Zhang D, Yin L, Robins DM: (2014) The KRAB Zinc Finger Protein RSL1 modulates sex-biased gene expression in liver and adipose tissue to maintain metabolic homeostasis. Molecular and Cellular Biology 34: 221-232.
Chua JP, Reddy SL, Merry DE, Adachi H, Katsuno M, Sobue G, Robins DM, Lieberman AP: (2014) Transcriptional activation of TFEB/ ZKSCAN3 target genes underlies enhanced autophagy in spinobulbar muscular atrophy. Human Molecular Genetics 23: 1376-86.
Krebs CJ, Schultz, Robins DM: (2012) The KRAB zinc finger protein RSL1 regulates sex- and tissue-specific promoter methylation and dynamic hormone-responsive chromatin configuration. Molecular and Cellular Biology 32: 3732-3742.
Yu Z, Wang AM, Robins DM, Lieberman AP: (2009) Altered RNA splicing contributes to skeletal muscle pathology in Kennedy disease knock-in mice. Disease Models and Mechanisms 2: 500-7.
Steinkamp MP, O’Mahony OA, Brogley M, Rehman H, LaPensee E, Dhanasekaran S, Hofer MD, Kuefer R, Chinnaiyan A, Rubin MA, Pienta KJ, Robins DM: (2009) Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Research 69:4434-4442.
Krebs CJ, Khan S, MacDonald JW, Sorenson M, Robins DM: (2009) The regulator of sex-limitation (Rsl) KRAB zinc finger proteins modulate sex-dependent and -independent liver metabolism. Physiological Genomics 38: 16-28.
Albertelli M, O’Mahony OA, Brogley M, Tosoian J, Steinkamp M, Daigneault S, Wojno K, Robins DM: (2008) Glutamine tract length of human androgen receptors affects both androgen-dependent and -independent prostate cancer in mice. Hum Mol Genetics 17: 98-110.