George B. Segel, M.D.

George B. Segel, M.D.

Contact Information

University of Rochester Medical Center
School of Medicine and Dentistry
601 Elmwood Ave, Box 704
Rochester, NY 14642

Office: (585) 275-3489
Fax: (585) 270-0350
Administrative: (585) 273--557

Research Bio

Dr. Segel's research interests are:
1) Chronic leukemia
2) Control of cell maturation
3) Early gene activation in chronic leukemia B lymphocytes induced toward a plasma cell phenotype



Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of lymphocytes that are arrested at an intermediate stage of B lymphocyte development. CLL B lymphocytes transform (mature) to a plasmacytic phenotype when treated in vitro with phorbol esters. We have used array hybridization technology to describe gene expression patterns for untreated and tetradecanoyl phorbol acetate (TPA)-treated CLL B-cells at 5, 10, and 20 minutes following initial TPA exposure. Three genes, Early Growth Response Factor 1 (EGR-1), dual specificity phosphatase 2, and CD69 (Early T-cell Activation Antigen), showed a 2.0-fold or greater increase in mRNA transcription at four or more of six time points in two studies. Upregulation of expression of these genes was confirmed by real-time polymerase chain reaction (RT-PCR) in the TPA-treated cells of four CLL patients.

A progressive increase in gene expression was observed during the 20 minute time course for all three genes. In addition, protein expression of EGR-1 and CD69 was increased as measured by immunofluorescence cell analysis. Several genes (PKC, n-myc, jun D, BCL-2) previously reported as overexpressed in CLL lymphocytes were overexpressed in these studies also, but were not altered by TPA treatment. Genes for proteins whose upregulation requires hours of TPA exposure (the 4F2hc component of the L-system amino acid transporter, prohibition, and hsp60) were assessed, and their later expression contrasted with the early expression of EGR-1, dual specificity phosphatase 2, and CD69. EGR-1 encodes a zinc-finger transcription factor that is induced by pokeweed mitogen and TPA and promotes B lymphocyte maturation.

The dual specificity phosphatase 2 encodes an enzyme that reverses mitogen activated protein (MAP) kinase cell activation by dephosphorylation. The CD69 protein is induced by TPA in thymocytes and is a type II transmembrane signaling molecule in hematopoietic cells. These findings suggest that the products of these three genes may be central to early steps in the TPA-induced evolution of CLL B-cells to a plasmacytic phenotype.

Awards & Honors (Local)

Teaching Award - Morning Report MVP Award | Award from the Pediatric and Med/Ped Residents | University of Rochester Medical Center, Rochester, NY 2011
Outstanding Hospital Teaching Award from the University of Rochester Third year class 2007 - 2008
Outstanding Hospital Teaching Award from the University of Rochester Fourth Year Class 2005 - 2006
Appointed to the Board of Directors for New York State, Genetics Task Force 1988 - 1992
Clara Barton Honor Award for Meritorious Volunteer Leadership, American Red Cross 1988
Certificate of Appreciation - American Red Cross Board of Directors 1982 - 1992
Buswell Distinguished Service Fellowship for Senior Faculty Support, University of Rochester 1981 - 1982
Faculty Service Award, Department of Pediatrics, University of Rochester 1981 - 1982
Recipient, Research Career Development Award U.S.P.H.S. #CA00019 1975 - 1980

Recent Journal Articles

Showing the 5 most recent journal articles. 90 available »

2011
Segel GB, Simon W and Lichtman MA. "Commentary: Should we still be focused on red cell hemolgobin F as the principal explanation for the salutary effect of hydroxyurea in sickle cell disease?". Pediatric Blood and Cancer. 2011; 57: 8-9.
2011
Bredlau AL, Semple JW and Segel GB. "Management of Idiopathic Thrombocytopenic Purpura in Children: Potential Role of Novel Agents." Pediatric Drugs. 2011; .
2010 Dec
Segel GB, Halterman MW, Lichtman MA. "The paradox of the neutrophil's role in tissue injury: a review." J Leukoc Biol.. 2010; .
2009
Segel GB and Feig SA. "Controversies in the Diagnosis and Management of Childhood Acute Immune Thrombocytopenic Purpura." Pediatric Blood and Cancer.. 2009; 53: 318-324. Link
2008 Jan
Segel GB, Halterman JS. "Neutropenia in pediatric practice." Pediatrics in review. 2008 Jan; 29(1):12-23; quiz 24.

Current Appointments

Professor Emeritus - Department of Pediatrics, Hematology and Oncology (SMD) - Primary

Specialties

Pediatrics - American Board of Pediatrics
Pediatric Hematology-Oncology - American Board of Pediatrics

Education

MD | Medicine | Jefferson Medical College1964

Post-Doctoral Training & Residency

Fellowship in Pediatric Hematology/Oncology at Children s Hospital07/01/1969 - 06/30/1971
Residency in Pediatrics at St Christopher's Hospital for Children07/01/1965 - 06/30/1967
Internship in Internal Medicine / Pediatrics at Abington Memorial Hospital07/01/1964 - 06/30/1965