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Haig H. Kazazian, Jr., M.D.

Photo of Dr. Haig H. Kazazian, Jr., M.D.

Professor of Pediatrics

Research Interests: Population genetics of active L1 retrotransposons in humans; Individual differences in retrotransposition capability have global effects on genome diversity and human evolution; A mouse model of human L1 retrotransposition as a tool for insertional mutagenesis and discovery of gene function; The SVA element is a non-autonomous retrotransposon that can cause disease; Preclinical trials of AAV-mediated gene therapy of hemophilia A in mice and dogs ...read more

Background

Dr. Haig Kazazian is a professor of pediatrics and molecular biology and genetics at the Johns Hopkins University School of Medicine.

A pioneering geneticist at Johns Hopkins, Dr. Kazazian was named as one of the first plaintiffs in the Supreme Court’s 2013 ruling that companies cannot patent parts of naturally occurring human genes.

 

Dr. Kazazian's lab focuses on the biology of LINE-1 (L1) retrotransposons in human beings and mice. They are also working on a second important project to carry out gene therapy of hemophilia A using AAV vectors. Recent research in the Kazazian lab has found actively “jumping genes” in humans, yielding new evidence that the genome contains numerous pesky mobile elements that may help to explain why people have such a variety of physical traits and disease risks. 

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Titles

  • Professor of Pediatrics
  • Professor of Molecular Biology and Genetics

Education

Degrees

  • M.D., Johns Hopkins University School of Medicine (Maryland) (1962)

Research & Publications

Research Summary

Over the past 22 years, the Kazazian lab has concentrated its efforts mainly on the biology of LINE-1 (L1) retrotransposons in human beings and mice. Retrotransposons are pieces of genomic DNA that have the ability to duplicate themselves and insert into a new genomic location. Over the years, we have found a number of human and mouse L1s insertions causing disease, including hemophilia A and muscular dystrophy. After finding the first such disease-causing insertions (1), we isolated the precursor (2) and devised a cell culture assay for retrotransposition (3). Using this assay, we have found that the average human diploid genome has 80-100 active L1 retrotransposons, but that most of the activity resides in a handful of very active or “hot” elements. We have also observed retrotransposition of human and mouse L1 elements in transgenic mice and rats, and found that most retrotransposition occurs not in germ cells but in the early embryo, resulting in somatic mosaicism (Reviewed in 4). Our most recent work utilizes the power of next generation DNA sequencing to locate essentially all human-specific L1s in any genome (5). This technique opens up the ability to answer many questions about L1 biology, including the frequency of somatic mosaicism in various human tissues and the role of L1 insertions in complex human disease, such as cancer and mental disorders.

A second important project has been an effort to carry out gene therapy of hemophilia A using AAV vectors. Hemophilia A is due to absence of the clotting factor, factor VIII. We have had considerable success in this endeavor in treating hemophilia A dogs, obtaining sustained therapeutic factor VIII levels for up to 5 years.

Lab Website: Haig Kazazian Lab

Selected Publications

View all on Pubmed

  1. Kazazian HH, Jr., Wong C, Yousoufian H, Scott AF, Phillips D, and Antonarakis SE: A novel mechanism of mutation in man: Hemophilia A due to de novo insertion of L1 sequences. Nature, 332:164-166, 1988.
  2. Dombroski BA, Mathias SL, Nanthakumar E, Scott AF, Kazazian HH, Jr. Isolation of an active human transposable element. Science 254:1805-1808, 1991.
  3. Moran JV, Holmes SE, Naas TP, DeBerardinis RJ, Boeke JD, and Kazazian HH, Jr. High frequency retro- transposition in cultured mammalian cells. Cell 87:917-927, 1996.
  4. Kano H, Godoy I, Courtney C, Merdiushev T, Gerton GL, Ostertag EM, and Kazazian HH, Jr. L1 retrotransposition occurs mainly in early embryogenesis and creates significant somatic mosaicism. Genes and Development 23:1303-12, 2009.
  5. Ewing AD and Kazazian HH, Jr. High-throughput sequencing reveals extensive variation in human-s[ecofoc L1 content in individual human genomes. Genome Research 20:1262-1270, 2010.

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