George Bertram Segel, M.D.

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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.

Specialty

Hematology / Oncology

Current Appointments

• Professor - Department of Pediatrics (SMD)
• Professor - Department of Medicine (SMD)

Education
MD Medicine	Jefferson Medical College	1964

Post-Doctoral Training & Residency
Academic Leave: Laboratory of Fred Sherman, PhD, Department of Biochemistry, University of Rochester School of Medicine, Rochester, NY	1991 - 1992
Pediatric Hematology/Oncology Fellowship, Childrens Hospital Medical Center, Harvard University Medical School, Boston, MA	1969 - 1971
Residency in Pediatrics, St. Christopher's Hospital for Children, Temple University, Philadelphia, PA	1965 - 1967
Rotating Internship, Abington Memorial Hospital, Abington, PA	1964 - 1965

Fellowship Awards
U.S.P.H.S. Grant #CA00019, Career Development, University of Rochester, Rochester, NY	1975 - 1980

Board Certifications
American Board of Pediatrics, Pediatric Hematology/Oncology	1974 - Present
American Board of Pediatrics	1969 - Present

Recent Journal Articles
Showing the 5 most recent journal articles. (87 available)
Segel GB and Feig SA. "Controversies in the Diagnosis and Management of Childhood Acute Immune Thrombocytopenic Purpura." Pediatric Blood and Cancer. 53 (2009): 318-324.
Segel GB; Halterman JS. "Neutropenia in pediatric practice." Pediatrics in review / American Academy of Pediatrics. 2008; 29(1):12-23; quiz 24.
Simon W, Segel GB and Lichtman MA. "Early allogeneic stem cell transplantation for chronic myelogeneous leukemia in the imatinib era: A preliminary assessment." Blood Cells, Molecules and Diseases. 37 (2006): 116-124.
Simon W; Segel GB; Lichtman MA. "Early allogeneic stem cell transplantation for chronic myelogenous leukemia in the imatinib era: a preliminary assessment." Blood cells, molecules & diseases. 2006; 37(2):116-24; discussion 125-7. Epub 2006 Aug 10.
Lichtman MA and Segel GB. "Uncommon Phenotypes of Acute Myelogeneous Leukemia: Basophilic, Mast Cell, Eosinophilic and Myeloid Dendritic Cell Subtypes: A review." Blood Cells, Molecules and Diseases 35 (2005): 370-383.