University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Aleksandar Rajkovic, MD, PhD

Aleksandar Rajkovic, MD, PhD

Chief Genomics Officer, UCSF Health; Professor, Dept. of Pathology, Dept. of Obstetrics, Gynecology and Reproductive Sciences, UCSF
Stuart Lindsay Distinguished Professor in Experimental Pathology

Cancer Center Program Memberships

Cancer Genetics

Research Summary

Aleksandar Rajkovic is a Professor of Pathology and Obstetrics/Gynecology and Reproductive Sciences. He is a Stuart Lindsay Distinguished Professor in Experimental Pathology I. He serves as the UCSF Chief Genomics Officer and is the Medical Director and Chief of the Center for Genetic and Genomic Medicine (CGGM) that organizes, coordinates and oversees Clinical Genetics and Genomics Services across the entire UCSF Health System. He also serves as the Director of the Genomic Medicine Initiative.

Rajkovic lab investigates the genetic underpinnings of the formation and differentiation of gametes and reproductive tract, their role of these genes in human disease, embryo lethality and origin of heritable human disorders. The lab studies transcriptional regulation of ovarian follicle activation and oocyte survival and how these processes are essential to produce healthy egg. Early stages of ovarian follicle formation, beginning with the breakdown of germ cell cysts, formation of primordial follicles and transition to primary and secondary follicles, are critical in determining the reproductive life span and fertility. Transcription of numerous germ cell specific genes, necessary and essential for follicular development, is initiated during these early stages of follicle formation. With mouse models, his laboratory discovered numerous transcriptional regulators such as Sohlh1, Sohlh2, Lhx8, and Nobox that regulate gamete development and reproductive tract development. These transcription factors are necessary to drive oocyte growth, and synthesis of maternal effect genes that are essential for early embryogenesis and are likely involved in setting of epigenetic marks. Mutations in these oocyte-specific transcriptional regulators associate with human condition of premature ovarian insufficiency and infertility, emphasizing the importance of these pathways to women’s health. Recent epidemiologic studies have suggested that reproductive tract development abnormalities and associated pathologies such as infertility, ovarian insufficiency and premature menopause are associated with higher mortality and morbidity. Whole genome human studies in his laboratory discovered that DNA damage repair genes such as MCM8 and MCM9 are mutated in women with infertility and the lab is exploring the link between DNA damage repair genes with infertility phenotypes and accelerated overall aging, as well as the effect of these genes on the overall health of offspring and genesis of structural birth defects. These and other studies indicate that many of the reproductive disorders are developmental in origin.

The lab is also investigating the genetic underpinnings of uterine leiomyomas, better known as fibroid tumors. Fibroid tumors are clinically apparent in nearly 25% of women by age 45, and they cause major morbidity in American women. We have discovered numerous genomic rearrangements that associate with this tumor and we also discovered that 70% of American women harbor mutations within one gene, MED12, regardless of the karyotype abnormality of the tumors. We are currently investigating the mechanisms of MED12 action in leiomyomas and therapies directed towards eliminating such tumors in symptomatic women.

The lab has also been at the forefront of applying cutting edge OMICS technologies to diagnosing infertility, gonadal dysgenesis, and prenatal disorders. The lab made significant contributions to non-invasive diagnosis of submicroscopic deletions, design and utility of dense X chromosome arrays, and utility of genomewide detection of copy number variants in prenatal diagnosis among others. The lab is currently investigating non-invasive OMICS both prior and post-implantation to predict and prevent human disorders.

Education

  • The Johns Hopkins University, BA, 05/85/ Chemistry
  • Case Western Reserve School of Medicine, PhD, 01/91, Molecular Biology
  • Case Western Reserve School of Medicine, MD, 05/92/ Doctor of Medicine

Professional Experience

  • 1992-1993
    Internship, Metrohealth Medical Center, Department of Internal Medicine
  • 1993-1996
    Resident, Obstetrics and Gynecology, Metrohealth Medical Center
  • 1996-1997
    Chief Resident, Obstetrics and Gynecology, Metrohealth Medical Center
  • 1997-1997
    Clinical Instructor, Dept of Obstetrics and Gynecology, Metrohealth Medical Center
  • 1997-2001
    Medical Genetics Fellow, Baylor College of Medicine, Human Genetics
  • 2001-2006
    Assistant Professor, Baylor College of Medicine, Department of Obstetrics and Gynecology
  • 2006-2009
    Associate Professor, Baylor College of Medicine, Department of Obstetrics and Gynecology
  • 2009-present
    Director of Reproductive Genetics, Magee Women’s Hospital, University of Pittsburgh
  • 2011-present
    Marcus Allen Hogge Chair in Reproductive Sciences, University of Pittsburgh
  • 2011-2013
    Associate Professor, Dept of Ob/Gyn and Reproductive Sciences, University of Pittsburgh
  • 2013-2018
    Professor, Graduate School of Public Health, Dept of Human Genetics, University of Pittsburgh
  • 2013-2018
    Professor, Dept of Pathology, University of Pittsburgh School of Medicine
  • 2013-2018
    Professor, Department of Ob/Gyn and Reproductive Sciences, University of Pittsburgh
  • 2018-present
    Distinguished Professor, Departments of Pathology, Obstetrics, Gynecology and Reproductive Sciences, UCSF

Honors & Awards

  • 1985
    Phi Beta Kappa
  • 1983
    American Chemical Society Award for Outstanding Achievement in Chemistry
  • 1997
    First Place Award, Research Day, Cleveland Society of Obstetrics and Gynecology
  • 1997
    Peter Adam Research Award, Metrohealth Medical Center, Cleveland, Ohio
  • 2013
    Elected to the American Society of Clinical Investigators (ASCI)
  • 2018
    Elected to American Association of Physicians (AAP)

Selected Publications

  1. Yatsenko SA, Rajkovic A. Genetics of human female infertility†. Biol Reprod. 2019 Sep 01; 101(3):549-566.
    View on PubMed
  2. Yatsenko SA, Wood-Trageser M, Chu T, Jiang H, Rajkovic A. A high-resolution X chromosome copy-number variation map in fertile females and women with primary ovarian insufficiency. Genet Med. 2019 Oct; 21(10):2275-2284.
    View on PubMed
  3. Gregg AR, Rajkovic A. Cell-Free DNA Screening During Pregnancy. JAMA. 2019 01 22; 321(3):308-309.
    View on PubMed
  4. Yang X, Touraine P, Desai S, Humphreys G, Jiang H, Yatsenko A, Rajkovic A. Gene variants identified by whole-exome sequencing in 33 French women with premature ovarian insufficiency. J Assist Reprod Genet. 2019 Jan; 36(1):39-45.
    View on PubMed
  5. Khan MJ, Pollock N, Jiang H, Castro C, Nazli R, Ahmed J, Basit S, Rajkovic A, Yatsenko AN. X-linked ADGRG2 mutation and obstructive azoospermia in a large Pakistani family. Sci Rep. 2018 11 02; 8(1):16280.
    View on PubMed
  6. Aarabi M, Kessler E, Madan-Khetarpal S, Surti U, Bellissimo D, Rajkovic A, Yatsenko SA. Autism spectrum disorder in females with ARHGEF9 alterations and a random pattern of X chromosome inactivation. Eur J Med Genet. 2019 Apr; 62(4):239-242.
    View on PubMed
  7. Portnoi MF, Dumargne MC, Rojo S, Witchel SF, Duncan AJ, Eozenou C, Bignon-Topalovic J, Yatsenko SA, Rajkovic A, Reyes-Mugica M, Almstrup K, Fusee L, Srivastava Y, Chantot-Bastaraud S, Hyon C, Louis-Sylvestre C, Validire P, de Malleray Pichard C, Ravel C, Christin-Maitre S, Brauner R, Rossetti R, Persani L, Charreau EH, Dain L, Chiauzzi VA, Mazen I, Rouba H, Schluth-Bolard C, MacGowan S, McLean WHI, Patin E, Rajpert-De Meyts E, Jauch R, Achermann JC, Siffroi JP, McElreavey K, Bashamboo A. Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies. Hum Mol Genet. 2018 04 01; 27(7):1228-1240.
    View on PubMed
  8. Katari S, Aarabi M, Kintigh A, Mann S, Yatsenko SA, Sanfilippo JS, Zeleznik AJ, Rajkovic A. Chromosomal instability in women with primary ovarian insufficiency. Hum Reprod. 2018 03 01; 33(3):531-538.
    View on PubMed
  9. Gurda GT, Serdy KM, Yatsenko SA, Rajkovic A, Carter NJ, Ahmed R, Olawaiye AB, Bhargava R, Elishaev E. Synchronous Bilateral Tubal Serous Carcinomas in a Patient With Exon 13 Duplication and Loss of Function of BRCA1. Int J Gynecol Pathol. 2018 Mar; 37(2):117-122.
    View on PubMed
  10. Aarabi M, Sniezek O, Jiang H, Saller DN, Bellissimo D, Yatsenko SA, Rajkovic A. Importance of complete phenotyping in prenatal whole exome sequencing. Hum Genet. 2018 Feb; 137(2):175-181.
    View on PubMed
  11. Richards JS, Ren YA, Candelaria N, Adams JE, Rajkovic A. Ovarian Follicular Theca Cell Recruitment, Differentiation, and Impact on Fertility: 2017 Update. Endocr Rev. 2018 02 01; 39(1):1-20.
    View on PubMed
  12. Ren Y, Diao F, Katari S, Yatsenko S, Jiang H, Wood-Trageser MA, Rajkovic A. Functional study of a novel missense single-nucleotide variant of NUP107 in two daughters of Mexican origin with premature ovarian insufficiency. Mol Genet Genomic Med. 2018 03; 6(2):276-281.
    View on PubMed
  13. Putra M, Surti U, Hu J, Steele D, Clemens M, Saller DN, Yatsenko SA, Rajkovic A. Beyond Down syndrome phenotype: Paternally derived isodicentric chromosome 21 with partial monosomy 21q22.3. Am J Med Genet A. 2017 Dec; 173(12):3153-3157.
    View on PubMed
  14. Rajkovic A, Pangas S. Ovary as a Biomarker of Health and Longevity: Insights from Genetics. Semin Reprod Med. 2017 05; 35(3):231-240.
    View on PubMed
  15. Shin YH, Ren Y, Suzuki H, Golnoski KJ, Ahn HW, Mico V, Rajkovic A. Transcription factors SOHLH1 and SOHLH2 coordinate oocyte differentiation without affecting meiosis I. J Clin Invest. 2017 Jun 01; 127(6):2106-2117.
    View on PubMed
  16. Dangle P, Touzon MS, Reyes-Múgica M, Witchel SF, Rajkovic A, Schneck FX, Yatsenko SA. Female-to-male sex reversal associated with unique Xp21.2 deletion disrupting genomic regulatory architecture of the dosage-sensitive sex reversal region. J Med Genet. 2017 10; 54(10):705-709.
    View on PubMed
  17. Desai S, Rajkovic A. Genetics of Reproductive Aging from Gonadal Dysgenesis through Menopause. Semin Reprod Med. 2017 03; 35(2):147-159.
    View on PubMed
  18. Desai S, Wood-Trageser M, Matic J, Chipkin J, Jiang H, Bachelot A, Dulon J, Sala C, Barbieri C, Cocca M, Toniolo D, Touraine P, Witchel S, Rajkovic A. MCM8 and MCM9 Nucleotide Variants in Women With Primary Ovarian Insufficiency. J Clin Endocrinol Metab. 2017 02 01; 102(2):576-582.
    View on PubMed
  19. Wang X, Mittal P, Castro CA, Rajkovic G, Rajkovic A. Med12 regulates ovarian steroidogenesis, uterine development and maternal effects in the mammalian egg. Biol Reprod. 2017 01 01; 97(6):822-834.
    View on PubMed
  20. Yatsenko SA, Mittal P, Wood-Trageser MA, Jones MW, Surti U, Edwards RP, Sood AK, Rajkovic A. Highly heterogeneous genomic landscape of uterine leiomyomas by whole exome sequencing and genome-wide arrays. Fertil Steril. 2017 02; 107(2):457-466.e9.
    View on PubMed

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