Aleksandar Rajkovic, PhD, MD
|School||School of Medicine|
|Address||513 Parnassus Avenue, HSW, #517|
San Francisco CA 94143
|Johns Hopkins University, Baltimore, Maryland||BS||1985||Chemistry|
|Case Western Reserve University, Cleveland, Ohio||MD/PhD||1992||Medicine/Molecular Biology|
|Metrohealth Medical Center, Cleveland, Ohio||Internship, General Medicine||1993||Internal Medicine|
|Metrohealth Medical Center, Cleveland, Ohio||Residency||1997||Obstetrics and Gynecology|
|Metrohealth Medical Cente, Cleveland, Ohio||Fellowship||1997||Maternal Fetal Medicine|
|Baylor College of Medicine, Houston, Texas||Medical Genetic Residency||1999||Medical Genetics|
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.
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