Kenneth H. Albrecht, Ph.D.

Kenn Albrecht, Ph.D.
Assistant Professor of Medicine
Assistant Professor of Genetics and Genomics
Director of Transgenic Core Facility
Boston University School of Medicine
Education
Post-doctoral Fellow, The Jackson Laboratory
1993 Ph.D. Genetics, The University of Connecticut
1986 B.S. Biology, SUNY Stony Brook
Other Appointments
Associate Director
BU Genome Science Institute
Graduate Program Affiliations
Cell and Molecular Biology
Genetics and Genomics
Molecular Medicine

 

Research Interests                                                                                                                                                                                        


xx_80 xyp_80 sprr_80 sry-egfp_80 sox9_80 pdgrfa_80
 

Mammalian gonadal sex determination is a powerful system for studying organogenesis, cell fate determination, and the evolution of sex chromosomes and developmental regulatory mechanisms. Besides basic scientific interest, mammalian sex determination also is of biomedical interest. Approximately one in 1000 infants has a gonadal or genital anomaly. Furthermore, many of the known genes involved in sex determination also are implicated in pathological processes such as tumorigenesis and primary adrenal failure, and have essential roles in the normal development of organs other than the gonads. We use the mouse as a model system for studying mammalian sex determination and gonad organogenesis and employ genetic, molecular genetic, genomic, cell biological and embryological techniques.

In mammals, XY fetuses develop testes due to the action of the Y-linked testis determining gene Sry (sex-determining region, Y chromosome) and XX fetuses develop ovaries in its absence. SRY is a DNA binding protein, and is likely a transcription factor that regulates other genes in the sex determination pathway. The mammalian gonadal precursors (the genital ridges) are bipotential and capable of differentiating as either testes or ovaries. It is generally accepted that each genital ridge contains a complete set of lineage precursors that are capable of adopting an ovarian or testicular cell-type fate. This “common precursor” hypothesis is best viewed as a series of bipotential cell fate decisions within the four cell lineages that comprise the gonad: germ cells, connective tissue cells, steroid producing cells and supporting cells. The current model proposes that Sry expression in the genital ridge initiates testis development by directing supporting cell precursors to develop as Sertoli rather than granulosa cells and that the development of all other gonadal cell types is dependent on the differentiation of the supporting cell lineage. Besides Sertoli cell differentiation, two direct consequences of Sry expression are the initiation of a male specific pattern of cell proliferation and the induction of mesenchymal cell migration from the adjacent mesonephros into the developing testis, a process necessary for testis cord development.

Although it is clear that expression of Sry is the trigger for testis differentiation, the molecular mechanisms of Sry function remain an enigma. For example, no downstream SRY target genes have been unequivocally identified and the regulation of Sry expression remains largely unexplored. A number of genes involved in gonadogenesis and sex determination have been identified and characterized; however, the position and relationship of these genes within the pathway remain to be defined and many more genes remain to be discovered. For example, most of the identified genes are transcription factors and not effector molecules. Additionally, our understanding of the genes involved in ovary development is particularly thin. Our future studies will include investigating the regulation of Sry expression, defining the position and relationship of known genes and identifying new genes in the gonad differentiation and sex determination pathways, and exploring basic mechanisms of gonad differentiation.


Selected Publications

  1. Wake C, Labadorf A, Dumitriu A, Hoss AG, Bregu J, Albrecht KH, DeStefano AL, Myers RH. Novel microRNA discovery using small RNA sequencing in post-mortem human brain. BMC Genomics. 2016 Oct 04; 17(1):776. PMID: 27716130.Read at: PubMed
  2. Correa SM, Washburn LL, Kahlon RS, Musson MC, Bouma GJ, Eicher EM, Albrecht KH. Sex reversal in C57BL/6J XY mice caused by increased expression of ovarian genes and insufficient activation of the testis determining pathway. PLoS Genet. 2012; 8(4):e1002569. PMID: 22496664.Read at: PubMed
  3. Pazin DE, Albrecht KH. Developmental expression of Smoc1 and Smoc2 suggests potential roles in fetal gonad and reproductive tract differentiation. Dev Dyn. 2009 Nov; 238(11):2877-90. PMID: 19842175.Read at: PubMed
  4. Lee HJ, Pazin DE, Kahlon RS, Correa SM, Albrecht KH. Novel markers of early ovarian pre-granulosa cells are expressed in an Sry-like pattern. Dev Dyn. 2009 Apr; 238(4):812-25. PMID: 19301398.Read at: PubMed
  5. Liu P, Pazin DE, Merson RR, Albrecht KH, Vaziri C. The developmentally-regulated Smoc2 gene is repressed by Aryl-hydrocarbon receptor (Ahr) signaling. Gene. 2009 Mar 15; 433(1-2):72-80. PMID: 19146932.Read at: PubMed
  6. Liu L, Brown D, McKee M, Lebrasseur NK, Yang D, Albrecht KH, Ravid K, Pilch PF. Deletion of Cavin/PTRF causes global loss of caveolae, dyslipidemia, and glucose intolerance. Cell Metab. 2008 Oct; 8(4):310-7. PMID: 18840361.Read at: PubMed
  7. Izvolsky KI, Lu J, Martin G, Albrecht KH, Cardoso WV. Systemic inactivation of Hs6st1 in mice is associated with late postnatal mortality without major defects in organogenesis. Genesis. 2008 Jan; 46(1):8-18. PMID: 18196599.Read at: PubMed
  8. Bouma GJ, Washburn LL, Albrecht KH, Eicher EM. Correct dosage of Fog2 and Gata4 transcription factors is critical for fetal testis development in mice. Proc Natl Acad Sci U S A. 2007 Sep 18; 104(38):14994-9. PMID: 17848526.Read at: PubMed
  9. Thevenet L, Albrecht KH, Malki S, Berta P, Boizet-Bonhoure B, Poulat F. NHERF2/SIP-1 interacts with mouse SRY via a different mechanism than human SRY. J Biol Chem. 2005 Nov 18; 280(46):38625-30. PMID: 16166090.Read at: PubMed
  10. Bouma GJ, Albrecht KH, Washburn LL, Recknagel AK, Churchill GA, Eicher EM. Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells. Development. 2005 Jul; 132(13):3045-54. PMID: 15944188.Read at: PubMed

 

Reviews

Albrecht KH and Eicher EM. 2002. Sex determination, mouse. In: Encyclopedia of Genetics, Brenner S, Miller JH (eds.). Academic Press, New York, pp. 1816-181.

Albrecht KH and Eicher EM. 2002. Mouse sex-reversed rearrangement. In: Encyclopedia of Genetics, Brenner S, Miller JH (eds.). Academic Press, New York, pp. 1253-12