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UCSF

ObGyn&RS

Center for Reproductive Sciences

Aleks Rajkovic
Aleksandar Rajkovic, MD, PhD

Chief Genomics Officer (CGO) of UCSF Health
Joint academic appointment as a UCSF professor in the departments of Pathology and of Obstetrics, Gynecology and Reproductive Sciences
Stuart Lindsay Distinguished Professor in Experimental Pathology

Research/Clinical Interests

Research interests lie in basic and translational medical sciences in the area of reproductive genetics, and in delivering non-invasive whole genome diagnostics both prior to and post-implantation. Research goals are to expand our understanding of genetic variants that affect women’s health, and to deliver better diagnostics for improved counseling and future therapies.

Education/Training

Year Institution & Location Degree Field of Study
1985 Johns Hopkins University, Baltimore BS Chemistry
1992 Case Western Reserve University, Cleveland MD/PHD Medicine & Molecular Biology
1997 Metrohealth Medical Center, Cleveland Residency Obstetrics and Gynecology
1997 Metrohealth Medical Center, Cleveland Fellowship Maternal-Fetal Medicine
1999 Baylor College of Medicine Medical Genetic Residency Medical Genetics

Achievements & Recognition

1985 Phi Beta Kappa Society
1985 American Chemical Society Award for Outstanding Achievement in Chemistry
1997 First Place Award, Research Day, Cleveland Society of Obstetrics & Gynecology
1997 Peter Adam Research Award
2013 Marcus Allen Hogge Chair in Reproductive Sciences, University of Pittsburgh
2013 Election to American Society for Clinical Investigation
2016 Keynote Speaker, International Federation of Fertility Societies

Selected Publications

Shin YH, Ren Y, Suzuki H, Golnoski KJ, Ahn HW, Mico V, Rajkovic A. (2017) Transcription Factors SOHLH2 Coordinate Differentiation without Affecting Meiosis l. J Clin Invest. 2017 May 15. pii:90281:10. 1172/JCI90281. PMID: 28504655

Previous studies have suggested that oocyte differentiation proceeds independent of meiosis. Although this has been suggested, it has never been shown how it happens and factors that drive it. In this manuscript, our group shows for the first time that Sohlh1 and Sohlh2 are the universal drivers of gamete differentiation independent of meiosis, and that these events are sexually dimorphic, as downstream pathways are different in female and male gonads, yet Sohlh1 and Sohlh2 are universal drivers. These findings are important considering efforts to differentiate oocytes from iPS cells and modify germline. Role: senior author, designed the research question, directed and interacted with postdocs and collaborators, co-wrote the manuscript.

Mittal P, Shin YH, Yatsenko SA, Castro CA, Surti U, Rajkovic A. (2015) Med12 gain-of-function mutation causes leiomyomas and genomic instability. J Clin Invest. 2015 Jul 20. pii: 81534. doi:10.1172/JCI81534. PubMed PMID: 26193636

We (PMID 22428002) and others have shown that 70% of uterine leiomyomas carry a variant in the exon 2 of Med12 gene. This association was intriguing but no experiments were conclusive that it is causative. Here we showed for the first time, that this variant causes uterine hyperplasia and leiomyomas in the mouse model, and that Med12 variant effects are gain of function and not due to loss of function. This publication has significant impact for other tumors, where variants in Med12 have recently been discovered, including breast phyllodes tumors and prostate cancer. Role: senior author, designed the research question, directed and interacted with postdocs and collaborators, co-wrote the manuscript.

AlAsiri S, Basit S, Wood-Trageser MA, Yatsenko SA, Jeffries EP, Surti U,Ketterer DM, Afzal S, Ramzan K, Faiyaz-Ul Haque M, Jiang H, Trakselis MA, Rajkovic A. (2014) Exome sequencing reveals MCM8 mutation underlies ovarian failure and chromosomal instability. J Clin Invest. Dec 1. pii: 78473. doi: 10.1172/JCI78473. PMID: 25437880

This paper shows for the first time that MCM8 mutations inherited in autosomal recessive fashion can cause gonadal dysgenesis and genomic instability. Previous menopause GWAS studies showed that SNPs in the MCM8 gene show some of the strongest association with menopause, however, whether this association was a true cause and effect with MCM8 or some surrounding genetic element was unknown. Our family based whole exome sequencing study as well as a follow up study (PMID:25480036) on its partner, MCM9, showed that MCM8 and MCM9 play a direct role in the spectrum of disorders from gonadal dysgenesis to premature menopause. Role: senior author, designed the research question, directed and interacted with postdocs and collaborators, co-wrote the manuscript.

Wood-Trageser MA, Gurbuz F, Yatsenko SA, Jeffries EP, Kotan LD, Surti U, Ketterer DM, Matic J, J, Jiang H, Trakselis MA, Topaloglu AK, Rajkovic A. (2014) MCM9 mutations are associated with ovarian failure, short stature, and chromosomal instability. Am J Hum Genet Dec 4;95(6):754-62. doi: 10.1016/j.ajhg.2014.11.002. PubMed PMID: 25480036; PubMed Central PMCID: PMC425997

We spent significant effort determining genetic causes of human gonadal failure, and this manuscript discovers MCM9 as a new gene involved in gonadal dysgenesis. Moreover, this gene causes chromosomal instability, just like MCM8, and has led to a hypothesis that a subset of women with infertility may have adverse medical events due to genetic variation at DNA damage response genes. These and other studies have opened investigation into the concept of fertility and overall health. Role: senior author, designed the research question, directed and interacted with postdocs and collaborators, co-wrote the manuscript.

Suzuki H, Ahn HW, Chu T, Bowden W, Gassei K, Orwig K, Rajkovic A. (2012) SOHLH1 and SOHLH2 coordinate spermatogonial differentiation. Dev Biol. 2012 Jan; 361(2):301-12. PubMed PMID: 22056784; PubMed Central PMCID: PMC3249242.

We previously discovered that Sohlh1 and Sohlh2 encode spermatogonia and oocyte specific helix-loop-helix transcriptional regulators, and in this manuscript, we showed that these two unique regulators physically interact and regulate spermatogonial differentiation as heterodimers. We also showed that SOHLH1 and SOHLH2 suppress genes involved in SSC maintenance, and induce genes important for spermatogonial differentiation. Role: senior author, designed the research question, directed and interacted with postdocs and collaborators, co-wrote the manuscript.