Aleksandar Rajkovic, PhD, MD

Chief Genomics Officer
M_Path-Anatomic Path
[email protected]
+1 415 502-4961

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.

Publications

Uterine Fibroids.

Physiological reviews

Bulun SE, Yin P, Wei JJ, Zuberi A, Iizuka T, Suzuki T, Saini P, Goad J, Parker JB, Adli M, Boyer T, Chakravarti D, Rajkovic A

Testis formation in XX individuals resulting from novel pathogenic variants in Wilms' tumor 1 (WT1) gene.

Proceedings of the National Academy of Sciences of the United States of America

Eozenou C, Gonen N, Touzon MS, Jorgensen A, Yatsenko SA, Fusee L, Kamel AK, Gellen B, Guercio G, Singh P, Witchel S, Berman AJ, Mainpal R, Totonchi M, Mohseni Meybodi A, Askari M, Merel-Chali T, Bignon-Topalovic J, Migale R, Costanzo M, Marino R, Ramirez P, Perez Garrido N, Berensztein E, Mekkawy MK, Schimenti JC, Bertalan R, Mazen I, McElreavey K, Belgorosky A, Lovell-Badge R, Rajkovic A, Bashamboo A

Mutations involving the SRY-related gene SOX8 are associated with a spectrum of human reproductive anomalies.

Human molecular genetics

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

Expansion of phenotype and genotypic data in CRB2-related syndrome.

European journal of human genetics : EJHG

Lamont RE, Tan WH, Innes AM, Parboosingh JS, Schneidman-Duhovny D, Rajkovic A, Pappas J, Altschwager P, DeWard S, Fulton A, Gray KJ, Krall M, Mehta L, Rodan LH, Saller DN, Steele D, Stein D, Yatsenko SA, Bernier FP, Slavotinek AM

Response to Sahoo et al.

Genetics in medicine : official journal of the American College of Medical Genetics

Yatsenko SA, Peters DG, Rajkovic A

Meta-analysis of loci associated with age at natural menopause in African-American women.

Human molecular genetics

Chen CT, Liu CT, Chen GK, Andrews JS, Arnold AM, Dreyfus J, Franceschini N, Garcia ME, Kerr KF, Li G, Lohman KK, Musani SK, Nalls MA, Raffel LJ, Smith J, Ambrosone CB, Bandera EV, Bernstein L, Britton A, Brzyski RG, Cappola A, Carlson CS, Couper D, Deming SL, Goodarzi MO, Heiss G, John EM, Lu X, Le Marchand L, Marciante K, Mcknight B, Millikan R, Nock NL, Olshan AF, Press MF, Vaiyda D, Woods NF, Taylor HA, Zhao W, Zheng W, Evans MK, Harris TB, Henderson BE, Kardia SL, Kooperberg C, Liu Y, Mosley TH, Psaty B, Wellons M, Windham BG, Zonderman AB, Cupples LA, Demerath EW, Haiman C, Murabito JM, Rajkovic A

Genome-wide association study of age at menarche in African-American women.

Human molecular genetics

Demerath EW, Liu CT, Franceschini N, Chen G, Palmer JR, Smith EN, Chen CT, Ambrosone CB, Arnold AM, Bandera EV, Berenson GS, Bernstein L, Britton A, Cappola AR, Carlson CS, Chanock SJ, Chen W, Chen Z, Deming SL, Elks CE, Evans MK, Gajdos Z, Henderson BE, Hu JJ, Ingles S, John EM, Kerr KF, Kolonel LN, Le Marchand L, Lu X, Millikan RC, Musani SK, Nock NL, North K, Nyante S, Press MF, Rodriquez-Gil JL, Ruiz-Narvaez EA, Schork NJ, Srinivasan SR, Woods NF, Zheng W, Ziegler RG, Zonderman A, Heiss G, Gwen Windham B, Wellons M, Murray SS, Nalls M, Pastinen T, Rajkovic A, Hirschhorn J, Adrienne Cupples L, Kooperberg C, Murabito JM, Haiman CA

A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.

PLoS genetics

Peters U, North KE, Sethupathy P, Buyske S, Haessler J, Jiao S, Fesinmeyer MD, Jackson RD, Kuller LH, Rajkovic A, Lim U, Cheng I, Schumacher F, Wilkens L, Li R, Monda K, Ehret G, Nguyen KD, Cooper R, Lewis CE, Leppert M, Irvin MR, Gu CC, Houston D, Buzkova P, Ritchie M, Matise TC, Le Marchand L, Hindorff LA, Crawford DC, Haiman CA, Kooperberg C

Family history of cancer and risk of pancreatic cancer: a pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).

International journal of cancer

Jacobs EJ, Chanock SJ, Fuchs CS, Lacroix A, McWilliams RR, Steplowski E, Stolzenberg-Solomon RZ, Arslan AA, Bueno-de-Mesquita HB, Gross M, Helzlsouer K, Petersen G, Zheng W, Agalliu I, Allen NE, Amundadottir L, Boutron-Ruault MC, Buring JE, Canzian F, Clipp S, Dorronsoro M, Gaziano JM, Giovannucci EL, Hankinson SE, Hartge P, Hoover RN, Hunter DJ, Jacobs KB, Jenab M, Kraft P, Kooperberg C, Lynch SM, Sund M, Mendelsohn JB, Mouw T, Newton CC, Overvad K, Palli D, Peeters PH, Rajkovic A, Shu XO, Thomas G, Tobias GS, Trichopoulos D, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu K, Zeleniuch-Jacquotte A

Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium.

Cancer research

Wolpin BM, Kraft P, Gross M, Helzlsouer K, Bueno-de-Mesquita HB, Steplowski E, Stolzenberg-Solomon RZ, Arslan AA, Jacobs EJ, Lacroix A, Petersen G, Zheng W, Albanes D, Allen NE, Amundadottir L, Anderson G, Boutron-Ruault MC, Buring JE, Canzian F, Chanock SJ, Clipp S, Gaziano JM, Giovannucci EL, Hallmans G, Hankinson SE, Hoover RN, Hunter DJ, Hutchinson A, Jacobs K, Kooperberg C, Lynch SM, Mendelsohn JB, Michaud DS, Overvad K, Patel AV, Rajkovic A, Sanchéz MJ, Shu XO, Slimani N, Thomas G, Tobias GS, Trichopoulos D, Vineis P, Virtamo J, Wactawski-Wende J, Yu K, Zeleniuch-Jacquotte A, Hartge P, Fuchs CS

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.

Nature genetics

Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, Arslan AA, Bueno-de-Mesquita HB, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Li D, Mandelson MT, Olson SH, Risch HA, Zheng W, Albanes D, Bamlet WR, Berg CD, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hassan M, Howard B, Hunter DJ, Hutchinson A, Jenab M, Kaaks R, Kooperberg C, Krogh V, Kurtz RC, Lynch SM, McWilliams RR, Mendelsohn JB, Michaud DS, Parikh H, Patel AV, Peeters PH, Rajkovic A, Riboli E, Rodriguez L, Seminara D, Shu XO, Thomas G, Tjønneland A, Tobias GS, Trichopoulos D, Van Den Eeden SK, Virtamo J, Wactawski-Wende J, Wang Z, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Fraumeni JF, Hoover RN, Hartge P, Chanock SJ

Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.

Nature genetics

Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA, Bueno-de-Mesquita HB, Gross M, Helzlsouer K, Jacobs EJ, LaCroix A, Zheng W, Albanes D, Bamlet W, Berg CD, Berrino F, Bingham S, Buring JE, Bracci PM, Canzian F, Clavel-Chapelon F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Fox JW, Gallinger S, Gaziano JM, Giovannucci EL, Goggins M, González CA, Hallmans G, Hankinson SE, Hassan M, Holly EA, Hunter DJ, Hutchinson A, Jackson R, Jacobs KB, Jenab M, Kaaks R, Klein AP, Kooperberg C, Kurtz RC, Li D, Lynch SM, Mandelson M, McWilliams RR, Mendelsohn JB, Michaud DS, Olson SH, Overvad K, Patel AV, Peeters PH, Rajkovic A, Riboli E, Risch HA, Shu XO, Thomas G, Tobias GS, Trichopoulos D, Van Den Eeden SK, Virtamo J, Wactawski-Wende J, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Chanock SJ, Hartge P, Hoover RN

Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2.

Nature genetics

Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Stratton MR, Rahman N, Jacobs K, Prentice R, Anderson GL, Rajkovic A, Curb JD, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver WR, Bojesen S, Nordestgaard BG, Flyger H, Dörk T, Schürmann P, Hillemanns P, Karstens JH, Bogdanova NV, Antonenkova NN, Zalutsky IV, Bermisheva M, Fedorova S, Khusnutdinova E, Kang D, Yoo KY, Noh DY, Ahn SH, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Garcia-Closas M, Lissowska J, Brinton L, Peplonska B, Nevanlinna H, Heikkinen T, Aittomäki K, Blomqvist C, Hopper JL, Southey MC, Smith L, Spurdle AB, Schmidt MK, Broeks A, van Hien RR, Cornelissen S, Milne RL, Ribas G, González-Neira A, Benitez J, Schmutzler RK, Burwinkel B, Bartram CR, Meindl A, Brauch H, Justenhoven C, Hamann U, Chang-Claude J, Hein R, Wang-Gohrke S, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Kataja V, Olson JE, Wang X, Fredericksen Z, Giles GG, Severi G, Baglietto L, English DR, Hankinson SE, Cox DG, Kraft P, Vatten LJ, Hveem K, Kumle M, Sigurdson A, Doody M, Bhatti P, Alexander BH, Hooning MJ, van den Ouweland AM, Oldenburg RA, Schutte M, Hall P, Czene K, Liu J, Li Y, Cox A, Elliott G, Brock I, Reed MW, Shen CY, Yu JC, Hsu GC, Chen ST, Anton-Culver H, Ziogas A, Andrulis IL, Knight JA, Beesley J, Goode EL, Couch F, Chenevix-Trench G, Hoover RN, Ponder BA, Hunter DJ, Pharoah PD, Dunning AM, Chanock SJ, Easton DF