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Harold C. Riethman

Wistar Institute Associate Professor of Genetics
Department: Genetics

Contact information
The Wistar Institute
36th & Spruce Sts.
Philadelphia, PA 19104
Office: 215-898-3872
B.S. (Biological Sciences)
University of Cincinnati, Cincinnati, OH, 1982.
M.S. (Biological Sciences)
University of Cincinnati, Cincinnati, OH, 1983.
Ph.D. (Biological Sciences)
University of Missouri, Columbia, MO, 1987.
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Description of Research Expertise

Dr. Harold Riethman is an Associate Professor in the Molecular and Cellular Oncogenesis Program at The Wistar Institute, and a Wistar Institute Associate Professor of Genetics at the University of Pennsylvania School of Medicine. He is also Associate Director of Training at The Wistar Institute. Dr. Riethman received his B.S. and M.S. in Biological Sciences from the University of Cincinnati. Following PhD work at the University of Missouri focused on the biochemistry and biophysics of photosynthetic light reactions, Dr. Riethman joined Maynard Olson’s lab at Washington University for postdoctoral work where he modified the recently-developed yeast artificial chromosome (YAC) cloning system to selectively capture large telomere-terminal fragments of human chromosomes. Upon establishment of his lab at The Wistar Institute, he expanded this work to create and characterize comprehensive clone libraries of human telomere regions. From 1991-2004 his lab played a key role in cloning, mapping, sequencing, and analysis of telomeric and subtelomeric DNA regions as part of the human genome project, collaborating with a wide range of both individual labs and large sequencing centers in the genome community in an interdisciplinary effort to accomplish this task. In particular, he led the effort to finish and annotate subtelomere regions, incorporating bioinformatic and computational approaches to classify and annotate subtelomeric segmental duplications and subterminal sequence features.

Currently, the Riethman laboratory focuses on the detailed characterization of genetic and epigenetic features of human subtelomeric and telomeric DNA as they relate to cancer and aging. This work is currently in two main areas. In the first, novel experimental and computational next-gen sequencing based approaches are being developed and used for analysis of subtelomeric structural variation, mutation, and annotation of human subtelomeric DNA. The Riethman laboratory, in collaboration with the Lieberman and Davuluri labs, has used existing next-gen datasets to annotate our updated human subtelomere sequence assemblies as part of an effort to understand the role of subtelomeric chromatin in the transcriptional regulation and function of a long noncoding RNA (TERRA) essential for telomere integrity (Deng et al., 2012). We have recently extended and refined our computational pipeline to enable efficient mapping of next-gen datasets to extended subtelomere DNA regions, where critically important genes are located and where previous analyses have been hampered by subtelomeric segmental duplication content. In the second area, the relationship of telomere length dynamics with telomere function and dysfunction is being investigated in several distinct contexts. Our laboratory is measuring telomere length as an environmentally-impacted biomarker associated with prostate cancer incidence and progression (collaboratively with Dr. T. Rebbeck and colleagues at University of Pennsylvania). In addition, we are developing both next-gen sequence-based and single-molecule fluorescence-based approaches to detect and characterize mutated and dysfunctional telomeres in cancer cells as well as in cells of individuals bearing constitutional ring chromosomes (collaboratively with Dr. Ming Xiao at Drexel and Dr. Nancy Spinner at CHOP).

Selected Publications

Deng Zhong, Wang Zhuo, Stong Nick, Plasschaert Robert, Moczan Aliah, Chen Horng-Shen, Hu Sufeng, Wikramasinghe Priyankara, Davuluri Ramana V, Bartolomei Marisa S, Riethman Harold, Lieberman Paul M: A role for CTCF and cohesin in subtelomere chromatin organization, TERRA transcription, and telomere end protection. The EMBO journal 31(21): 4165-78, Nov 2012.

Conlin Laura K, Kramer Whitney, Hutchinson Anne L, Li Xia, Riethman Harold, Hakonarson Hakon, Mulley John C, Scheffer Ingrid E, Berkovic Samuel F, Hosain Syed A, Spinner Nancy B: Molecular analysis of ring chromosome 20 syndrome reveals two distinct groups of patients. Journal of medical genetics 48(1): 1-9, Jan 2011.

Descipio Cheryl, Morrissette Jennifer D, Conlin Laura K, Clark Dinah, Kaur Maninder, Coplan James, Riethman Harold, Spinner Nancy B, Krantz Ian D: Update on "two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of chromosome 20". American journal of medical genetics. Part A 152A(6): 1599, Jun 2010.

Descipio Cheryl, Morrissette Jennifer D, Conlin Laura K, Clark Dinah, Kaur Maninder, Coplan James, Riethman Harold, Spinner Nancy B, Krantz Ian D: Two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of chromosome 20. American journal of medical genetics. Part A 152A(2): 373-82, Feb 2010.

Butts Samantha, Riethman Harold, Ratcliffe Sarah, Shaunik Alka, Coutifaris Christos, Barnhart Kurt: Correlation of telomere length and telomerase activity with occult ovarian insufficiency. The Journal of clinical endocrinology and metabolism 94(12): 4835-43, Dec 2009.

Deng Zhong, Norseen Julie, Wiedmer Andreas, Riethman Harold, Lieberman Paul M: TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Molecular cell 35(4): 403-13, Aug 2009.

Lou Zhenjun, Wei Jun, Riethman Harold, Baur Joseph A, Voglauer Regina, Shay Jerry W, Wright Woodring E: Telomere length regulates ISG15 expression in human cells. Aging 1(7): 608-21, Jul 2009.

Riethman H: Human Telomere Structure and Biology. Annu Rev Genomics Hum Genet. May 2008.

DeScipio Cheryl, Spinner Nancy B, Kaur Maninder, Yaeger Dinah, Conlin Laura K, Ambrosini Anthony, Hu Sufen, Shan Simei, Krantz Ian D, Riethman Harold: Fine-mapping subtelomeric deletions and duplications by comparative genomic hybridization in 42 individuals. American journal of medical genetics. Part A 146A(6): 730-9, Mar 2008.

Tsipouri Vicky, Schueler Mary G, Hu Sufen, Dutra Amalia, Pak Evgenia, Riethman Harold, Green Eric D: Comparative sequence analyses reveal sites of ancestral chromosomal fusions in the Indian muntjac genome. Genome biology 9(10): R155, 2008.

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Last updated: 12/12/2012
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