Areas of Interest
We study gene regulation by steroid hormones, focusing on transcriptional mechanisms, hormone-dependent cancers, and sex-dependent gene modulation. Steroid receptors are ligand-activated transcription factors with diverse functions, yet several act via common DNA binding sites and interact with common coregulators. We examine how specific gene control 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 allows us to study mechanisms of treatment resistance, particularly by somatic AR mutation. In both mouse and human tumors, AR mutants use diverse mechanisms to evade therapy. We are using Next Generation Sequencing to profile differential gene expression and alternative regulatory networks, to improve prognosis and anti-AR treatments.
Sex differences in gene expression occur widely, impacting physiology and incidence of many diseases. We identified via 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
- 2015 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.
Higgins J, Brogley M, Palanisamy N, Mehra R, Ittmann MM, Li JZ, Tomlins SA, Robins DM: (2015) Interaction of the androgen receptor, ETV1, and PTEN pathways in mouse prostate varies with pathological stage and predicts cancer progression. Hormones and Cancer 6: 67-86.
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: (2013) Transcriptional activation of TFEB/ZKSCAN3 target genes underlies enhanced autophagy in spinobulbar muscular atrophy. Human Molecular Genetics (epub ahead of print).
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.
Robins DM: (2012) Androgen receptor gene polymorphisms and alterations in prostate cancer: of humanized mice and men. Molecular and Cellular Endocrinology 16: 26-33.
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.
O'Mahony OA, Steinkamp MP, Albertelli MA, Brogley M, Rehman H, Robins DM: (2008) Profiling human androgen receptor mutations reveals treatment effects in a mouse model of prostate cancer. Molecular Cancer Research 6: 1691-1701.
Albertelli MA, 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. Human Molecular Genetics 17: 98-110.
Albertelli MA, Scheller A, Brogley M, Robins DM: (2006) Replacing the mouse androgen receptor with human alleles demonstrates glutamine tract length dependent effects on physiology and tumorigenesis in mice. Molecular Endocrinology, 20:1248-1260.
Krebs CJ, Larkins LK, Khan SM, Robins DM: (2005) Expansion and diversification of KRAB zinc-finger genes within a cluster including Regulator of sex-limitation 1 and 2. Genomics 85: 752-761
Krebs CJ, Larkins LK, Price R, Tullis KM, Miller RD, Robins DM: (2003) Regulator of sex-limitation (Rsl) encodes a pair of KRAB zinc-finger genes that control sexually dimorphic liver gene expression. GenesDev. 17: 2664-2674.