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Carmen Sapienza, PhD

Professor of Pathology

Associate Director, Fels Institute for Cancer Research

and Molecular Biology

Telephone:  215-707-7373

Fax:  215-707-6989

Email: sapienza@temple.edu

Fels Institute for Cancer Research and Molecular Biology

Department of Pathology and Laboratory Medicine

PhD (1982), Dalhousie University (Halifax, Nova Scotia, Canada)

 

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My laboratory investigates mechanisms that result in exceptions to Mendel’s laws of inheritance. We are studying genetic alterations that may result in defects in maternal/paternal chromosome imprinting in both human and mouse. The potential relationship between failure to maintain maternal/paternal distinctions between chromosomes and the processes of chromosome pairing, recombination and segregation, as well as susceptibility to cancer, is being addressed in human families and in the mouse. We have also observed that “imprints” and other epigenetic marks, such as X-chromosome inactivation, can become unstable with age. We propose that “loss of imprinting” and other epigenetic marks leads to genetic instability and cancer in some tissues, such as colon mucosa, but may be associated with the death of particular classes of stem cells (such as in the hematopoietic system) at advanced age.

We are also investigating whether environmental factors may alter epigenetic marks. One of the most potentially disruptive environments to which human beings are exposed is the in vitro culture conditions associated with assisted reproductive techniques (in vitro fertilization and intracytoplasmic sperm injection). Epidemiological studies suggest that children born through assisted reproduction are at substantially increased risk for several rare diseases associated with defects in epigenetic marking of the genome. We are in the process of examining several measures of epigenetic marking in children conceived in vitro and in vivo.

The laboratory also has a long-standing interest in the polar, preimplantation-lethal phenotype known as “DDK syndrome”. This phenomenon occurs when females of the DDK inbred strain are mated to males of many other inbred strains and results in the death of 95% of the hybrid embryos between the 8-cell and blastocyst stage. We have mapped the genetic determinant(s) of this phenotype to a 650 kb region of mouse chromosome 11 and are examining the expression of candidate genes in this region. We have also described an association between this parental origin-specific phenotype and a non-random effect on the meiotic segregation of chromosome 11 during female meiosis.

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Recent Medically Related Publications, Obtained from PubMed (Click on PubMed ID to view abstract)

19605411. Katari S, Turan N, Bibikova M, Erinle O, Chalian R, Foster M, Gaughan JP, Coutifaris C, Sapienza C, DNA methylation and gene expression differences in children conceived in vitro or in vivo. Hum Mol Genet 18:20(3769-78)2009 Oct 15

19229137. Engel N, Tront JS, Erinle T, Nguyen N, Latham KE, Sapienza C, Hoffman B, Liebermann DA, Conserved DNA methylation in Gadd45a(-/-) mice. Epigenetics 4:2(98-9)2009 Feb

19129515. Hao L, Vassena R, Wu G, Han Z, Cheng Y, Latham KE, Sapienza C, The unfolded protein response contributes to preimplantation mouse embryo death in the DDK syndrome. Biol Reprod 80:5(944-53)2009 May

18562704. Han Z, Mtango NR, Patel BG, Sapienza C, Latham KE, Hybrid vigor and transgenerational epigenetic effects on early mouse embryo phenotype. Biol Reprod 79:4(638-48)2008 Oct

17204629. Sapienza C, Molecular biology. Do Watson and Crick motor from X to Z? Science 315:5808(46-7)2007 Jan 5

16839189. Sandovici I, Kassovska-Bratinova S, Vaughan JE, Stewart R, Leppert M, Sapienza C, Human imprinted chromosomal regions are historical hot-spots of recombination. PLoS Genet 2:7(e101)2006 Jul

16172501. Bell TA, de la Casa-Esperón E, Doherty HE, Ideraabdullah F, Kim K, Wang Y, Lange LA, Wilhemsen K, Lange EM, Sapienza C, de Villena FP, The paternal gene of the DDK syndrome maps to the Schlafen gene cluster on mouse chromosome 11. Genetics 172:1(411-23)2006 Jan

15972727. Sandovici I, Kassovska-Bratinova S, Loredo-Osti JC, Leppert M, Suarez A, Stewart R, Bautista FD, Schiraldi M, Sapienza C, Interindividual variability and parent of origin DNA methylation differences at specific human Alu elements. Hum Mol Genet 14:15(2135-43)2005 Aug 1

15868680. Latham KE, Sapienza C, Developmental potential as a criterion for understanding and defining embryos. Conn Law Rev 36:4(1171-6)2004 Summer

15744049. Wu G, Hao L, Han Z, Gao S, Latham KE, de Villena FP, Sapienza C, Maternal transmission ratio distortion at the mouse Om locus results from meiotic drive at the second meiotic division. Genetics 170:1(327-34)2005 May

15483220. Gao S, Wu G, Han Z, de la Casa-Esperón E, Sapienza C, Latham KE, Recapitulation of the ovum mutant (Om) phenotype and loss of Om locus polarity in cloned mouse embryos. Biol Reprod 72:2(487-91)2005 Feb

15338278. Sandovici I, Naumova AK, Leppert M, Linares Y, Sapienza C, A longitudinal study of X-inactivation ratio in human females. Hum Genet 115:5(387-92)2004 Oct

14616065. de la Casa-Esperón E, Sapienza C, Natural selection and the evolution of genome imprinting. Annu Rev Genet 37:(349-70)2003

12812984. Sandovici I, Leppert M, Hawk PR, Suarez A, Linares Y, Sapienza C, Familial aggregation of abnormal methylation of parental alleles at the IGF2/H19 and IGF2R differentially methylated regions. Hum Mol Genet 12:13(1569-78)2003 Jul 1

12196408. de La Casa-Esperón E, Loredo-Osti JC, Pardo-Manuel de Villena F, Briscoe TL, Malette JM, Vaughan JE, Morgan K, Sapienza C, X chromosome effect on maternal recombination and meiotic drive in the mouse. Genetics 161:4(1651-9)2002 Aug

12149520. Sapienza C, Imprinted gene expression, transplantation medicine, and the "other" human embryonic stem cell. Proc Natl Acad Sci U S A 99:16(10243-5)2002 Aug 6

11309665. Pardo-Manuel de Villena F, Sapienza C, Recombination is proportional to the number of chromosome arms in mammals. Mamm Genome 12:4(318-22)2001 Apr

11214904. Pardo-Manuel de Villena F, Sapienza C, Transmission ratio distortion in offspring of heterozygous female carriers of Robertsonian translocations. Hum Genet 108:1(31-6)2001 Jan

11102708. Pardo-Manuel de Villena F, de la Casa-Esperón E, Sapienza C, Natural selection and the function of genome imprinting: beyond the silenced minority. Trends Genet 16:12(573-9)2000 Dec

10790402. Pardo-Manuel De Villena F, de La Casa-Esperón E, Williams JW, Malette JM, Rosa M, Sapienza C, Heritability of the maternal meiotic drive system linked to Om and high-resolution mapping of the Responder locus in mouse. Genetics 155:1(283-9)2000 May

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