Skip to main content
Explore URMC

URMC Logo

menu

Robert Stanley Freeman, Ph.D.

Contact Information

Phone Numbers

Appointment: (585) 276-3000

Research Labs

Biography

Research

During development of the nervous system, as many as half of all neurons generated are ultimately eliminated by a process known as programmed cell death. Much of this cell death occurs as newly differentiated neurons compete for limiting amounts of survival-promoting 'neurotrophic' factors. Though counterintuitive, the selective death of neurons at specific times during development is critical for sculpting a properly wired nervous system. While programmed cell death is essential for normal development, too much or too little cell death later in life is a confounding factor in diseases ranging from Alzheimer's disease and stroke to brain cancer. Research in the Freeman laboratory is aimed at characterizing the mechanisms that regulate cell death in the mammalian nervous system. More specifically, we aim to identify and understand the critical cell signaling events that, if left unchecked, commit a neuron to die.

Our basic approach involves comparing gene expression and protein function in neurons before and after exposure to a death-inducing stimulus. For example, to study programmed cell death during development, we use a model in which neurons are deprived of the neurotrophic factor nerve growth factor. Using this model, we have discovered new roles during cell death for two proline-modifying enzymes, the prolyl hydroxylase EGLN3 and the peptidyl-prolyl isomerase PIN1. Using techniques and approaches from cell and molecular biology, genetics, and biochemistry, we are (1) determining the effects of knocking out these proteins on cell death during development and disease, (2) identifying their biochemical targets and substrates, and (3) characterizing the pathways that regulate their function in dying neurons.

A second interest of the laboratory concerns the mechanisms by which oxygen availability regulates the survival of developing neurons. Prenatal or perinatal hypoxia and hypoxia-ischemia are important causes of neonatal brain injury and abnormal brain development. To better understand these processes, we are investigating the regulation and function of the hypoxia-inducible factor (HIF) family of transcription factors in neurons exposed to different oxygen tensions. Ultimately, our research efforts are driven by the prospect that the mechanisms we uncover may ultimately contribute to the development of new therapies for cell death-related diseases and disorders of the nervous system.

Credentials

Faculty Appointments

Education

1985
BS | University of Delaware
Chemistry

1991
PhD | Univ of Cal San Diego
Biochemistry

Awards

2008
Alumni Award for Excellence in Graduate Education
Location: University of Rochester

1996 - 2000
Paul Stark Professorship in Pharmacology
Location: University of Rochester

1992 - 1994
NRSA Postdoctoral Fellowship
Sponsor: NIH/NINDS
Location: Washington University School of Medicine

VIEW ALL expand_more

Publications

Journal Articles

5/2012
Fernandes KA, Harder JM, Fornarola LB, Freeman RS, Clark AF, Pang IH, John SW, Libby RT. "JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death." Neurobiology of disease.. 2012 May 0; 46(2):393-401. Epub 2012 Feb 14.

2/3/2011
Guo H, Barrett TM, Zhong Z, Fernandez JA, Griffin JH, Freeman RS, Zlokovic BV. "Protein S blocks the extrinsic apoptotic cascade in tissue plasminogen activator/N-methyl D-aspartate-treated neurons via Tyro3-Akt-FKHRL1 signaling pathway." Molecular neurodegeneration. 2011 Feb 3; 6:13. Epub 2011 Feb 03.

11/17/2010
Zhong Z, Wang Y, Guo H, Sagare A, Fernández JA, Bell RD, Barrett TM, Griffin JH, Freeman RS, Zlokovic BV. "Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding globulin-like region." The Journal of neuroscience : the official journal of the Society for Neuroscience.. 2010 Nov 17; 30(46):15521-34.

Books & Chapters

1998
Chapter Title: The cell cycle and neuronal cell death
Book Title: Cell Death in Diseases of the Nervous System
Author List: R. S. Freeman
Edited By: V. Koliatsos and R. R. Ratan
Published By: Humana Press Inc1998 in Totowa, NJ

1993
Chapter Title: Molecular mechanism of programmed cell death in the developing nervous system
Book Title: Neuronal Cell Death and Repair
Author List: E. M. Johnson, Jr., E. B. Cornbrooks, T. L. Deckwerth, S. Estus, J. L. Franklin, R. S. Freeman, K. Horigome and P. A. Lampe
Edited By: A. C. Cuello
Published By: Elsevier Science Publishers1993 in Amsterdam

VIEW ALL PUBLICATIONS