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George B. Segel, M.D.

Contact Information

Phone Numbers

Administrative: (585) 273--557

Office: (585) 275-3489

Fax: (585) 270-0350

URMFGA member of the University of Rochester Medical Faculty Group

groupAn Accountable Health Partner

assignmentNot Accepting New Patients

Faculty Appointments

Patient Care Setting

Cancer

Biography

Anemia, Neutropenia, Thrombocytopenia and Other Hematologic Disorders including hemostasis and thrombosis. Consultation for hematologic disorders on Pediatrics and Internal Medicine.

Research

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.

Credentials

Education

1964
MD | Jefferson Medical College

Post-doctoral Training & Residency

07/01/1969 - 06/30/1971
Fellowship in Pediatric Hematology-Oncology at Children's Hospital of Boston

07/01/1965 - 06/30/1967
Residency in Pediatrics at St. Christophers Hospital for Children GME

07/01/1964 - 06/30/1965
Internship in Pediatrics, Internal Medicine at Abington Memorial Hospital

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Awards

2011
Teaching Award - Morning Report MVP Award
Sponsor: Award from the Pediatric and Med/Ped Residents
Location: University of Rochester Medical Center, Rochester, NY

2007 - 2008
Outstanding Hospital Teaching Award from the University of Rochester Third year class

2005 - 2006
Outstanding Hospital Teaching Award from the University of Rochester Fourth Year Class

1988 - 1992
Appointed to the Board of Directors for New York State, Genetics Task Force

1988
Clara Barton Honor Award for Meritorious Volunteer Leadership, American Red Cross

1982 - 1992
Certificate of Appreciation - American Red Cross Board of Directors

1981 - 1982
Buswell Distinguished Service Fellowship for Senior Faculty Support, University of Rochester

1981 - 1982
Faculty Service Award, Department of Pediatrics, University of Rochester

1975 - 1980
Recipient, Research Career Development Award U.S.P.H.S. #CA00019

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Publications

Journal Articles

2011
Segel GB, Simon W and Lichtman MA. "Commentary: Should we still be focused on red cell hemoglobin 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; .

12/2010
Segel GB, Halterman MW, Lichtman MA. "The paradox of the neutrophil's role in tissue injury: a review." J Leukoc Biol. 2010; .

Books & Chapters

2011
Chapter Title: A Practical Guide for Clinicians
Book Title: Chronic Complex Diseases of Childhood
Author List: Segel GB, Feig SA and Morimoto K.
Edited By: Yazdani S, McGhee SA and Stiehm R.
Published By: Brown Walker Press 2011 in Boca Raton, FLA

2011
Chapter Title: Lymphadenopathy
Book Title: Textbook of Pediatric Care, 2nd Edition
Author List: Segel GB and Hall C.
Edited By: McInerny TK, Adam HK, Campbell D, Kamat DK and Kelleher KJ.
Published By: American Academy of Pediatrics 2011 in Elk Grove, Ill

2010
Chapter Title: Hemolytic Anemias (introduction): Hereditary Spherocytosis; Hereditary Elliptocytosis; Hereditary Stomatocytosis: Other Membrane Defects:
Book Title: Nelson Textbook of Pediatrics, 19th edition.
Author List: Segel GB
Edited By: Behrman, Kleigman, Nelson, Vaughan (Editors)
Published By: WB Saunders Co. 2010

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