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Mark I. Greene, MD, PhD, FRCP
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Emeritus Professor of Pathology and Laboratory Medicine
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Department: Pathology and Laboratory Medicine
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Graduate Group Affiliations
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- Cell and Molecular Biology 5c
- Immunology e
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Contact information
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252 John Morgan Building
35 3620 Hamilton Walk
Philadelphia, PA 19104
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35 3620 Hamilton Walk
Philadelphia, PA 19104
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Office: (215) 898-2847
34 Fax: (215) 898-2401
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34 Fax: (215) 898-2401
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Email:
GREENE@REO.MED.UPENN.EDU
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GREENE@REO.MED.UPENN.EDU
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Publications
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Education:
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37 University of Manitoba, Canada, 1968.
21 9 M.D. c
37 University of Manitoba, Canada, 1972.
21 5 13 (Intern) c
41 Health Sciences Centre, Winnipeg, Canada, 1973.
21 5 15 (Resident) c
41 Health Sciences Centre, Winnipeg, Canada, 1976.
21 c F.R.C.P 1e (Internal Medicine) c
4b Fellow of the Royal College of Physicians (Canada), 1976.
21 a Ph.D. 17 (Immunology) c
37 University of Manitoba, Canada, 1977.
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21 5 c
37 University of Manitoba, Canada, 1968.
21 9 M.D. c
37 University of Manitoba, Canada, 1972.
21 5 13 (Intern) c
41 Health Sciences Centre, Winnipeg, Canada, 1973.
21 5 15 (Resident) c
41 Health Sciences Centre, Winnipeg, Canada, 1976.
21 c F.R.C.P 1e (Internal Medicine) c
4b Fellow of the Royal College of Physicians (Canada), 1976.
21 a Ph.D. 17 (Immunology) c
37 University of Manitoba, Canada, 1977.
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Links
99 Search PubMed for articles
42 Pharmacological Sciences graduate group faculty webpage.
45 Cell and Molecular Biology graduate group faculty webpage.
42 Immunology graduate group faculty webpage.
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Permanent link99 Search PubMed for articles
42 Pharmacological Sciences graduate group faculty webpage.
45 Cell and Molecular Biology graduate group faculty webpage.
42 Immunology graduate group faculty webpage.
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50 Receptor function, small molecules, centrosome and associated proteins.
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37 Key words: Receptors, cancer, structure.
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26 Description of Research
2a9 Dr. Greene's research is concerned with defining the principles of receptor function. An area he has concentrated on for the last 19 years involves members of the erbB gene family. Greene's laboratory discovered that pl85c-neu could associate with EGFR to form a heteromeric assembly. This heteromeric complex possessed unique properties including increased kinase activity. The heterodimers had a higher affinity for EGF than homomeric forms of the EGFR receptor and were found to represent the major signaling receptor form. Heteromer formation was found to be preferred over homomeric assembly and the ectodomains were found essential in stabilizing the dimeric species.
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312 Greene's laboratory developed an approach to target and down-modulate oncoproteins which when expressed were critical for abnormal growth. This simple approach developed in the neu system involved developing monoclonal antibodies specific for the ectodomain of pl85. The approach was to take advantage of the formation of kinase active homomeric (pl85-pl85) or heteromeric (pl85c-neu-EGFr) assemblies found on malignant cells and which were active in mediating the transformed phenotype. Normal receptor species which are not activated are in a kinase inactive configuration. Furthermore, down modulation of normal receptors is not associated with cell injury. This was the basis for targeted therapy and the approach has led to an improved treatment for advanced breast cancer.
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169 Greene has recently begun to design organic molecules that disable protein function. His laboratory uses crystallography and thermodynamic analyses to help define cavities near active sites that are used to lodge organic molecules. These cavity filling molecules induce allosteric changes in the active sites leading to modification of protein function.
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178 As part of the studies to define the progression of the transformed phenotype, Greene's laboratory has focused on the assembly and function of the mammalian centrosome. His group has identified several new genes that encode centrosomal proteins that appear relevant to the centrosome assembly pathway. Certain of these genes are also relevant to the spindle checkpoint.
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Description of Research Expertise
2b Research Interests50 Receptor function, small molecules, centrosome and associated proteins.
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37 Key words: Receptors, cancer, structure.
8
26 Description of Research
2a9 Dr. Greene's research is concerned with defining the principles of receptor function. An area he has concentrated on for the last 19 years involves members of the erbB gene family. Greene's laboratory discovered that pl85c-neu could associate with EGFR to form a heteromeric assembly. This heteromeric complex possessed unique properties including increased kinase activity. The heterodimers had a higher affinity for EGF than homomeric forms of the EGFR receptor and were found to represent the major signaling receptor form. Heteromer formation was found to be preferred over homomeric assembly and the ectodomains were found essential in stabilizing the dimeric species.
8
312 Greene's laboratory developed an approach to target and down-modulate oncoproteins which when expressed were critical for abnormal growth. This simple approach developed in the neu system involved developing monoclonal antibodies specific for the ectodomain of pl85. The approach was to take advantage of the formation of kinase active homomeric (pl85-pl85) or heteromeric (pl85c-neu-EGFr) assemblies found on malignant cells and which were active in mediating the transformed phenotype. Normal receptor species which are not activated are in a kinase inactive configuration. Furthermore, down modulation of normal receptors is not associated with cell injury. This was the basis for targeted therapy and the approach has led to an improved treatment for advanced breast cancer.
8
169 Greene has recently begun to design organic molecules that disable protein function. His laboratory uses crystallography and thermodynamic analyses to help define cavities near active sites that are used to lodge organic molecules. These cavity filling molecules induce allosteric changes in the active sites leading to modification of protein function.
8
178 As part of the studies to define the progression of the transformed phenotype, Greene's laboratory has focused on the assembly and function of the mammalian centrosome. His group has identified several new genes that encode centrosomal proteins that appear relevant to the centrosome assembly pathway. Certain of these genes are also relevant to the spindle checkpoint.
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