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Robert Stanley Freeman, Ph.D.

Contact Information

Phone Numbers

Office: (585) 273-4893

Fax: (585) 273-2652

Research Labs

Faculty Appointments



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.



BS | University of Delaware

PhD | Univ of Cal San Diego

Post-doctoral Training & Residency

1991 - 1994
Washington University School of Medicine, Department of Molecular Biology and Pharmacology. Mentor: Eugene M. Johnson, Ph.D.


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

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Journal Articles

Peng H, Purkerson JM, Freeman RS, Schwaderer AL, Schwartz GJ. "Acidosis induces antimicrobial peptide expression and resistance to uropathogenic infection in kidney collecting duct cells via HIF-1?." American journal of physiology. Renal physiology.. 2020 Feb 1; 318(2):F468-F474. Epub 2019 Dec 16.

Papasergi-Scott MM, Stoveken HM, MacConnachie L, Chan PY, Gabay M, Wong D, Freeman RS, Beg AA, Tall GG. "Dual phosphorylation of Ric-8A enhances its ability to mediate G protein ? subunit folding and to stimulate guanine nucleotide exchange." Science signaling.. 2018 May 29; 11(532)Epub 2018 May 29.

Bellizzi MJ, Hammond JW, Li H, Gantz Marker, Marker DF, Freeman RS, Gelbard HA. "The Mixed-Lineage Kinase Inhibitor URMC-099 Protects Hippocampal Synapses in Experimental Autoimmune Encephalomyelitis." eNeuro.. 2018 5(6)Epub 2018 Dec 03.

Books & Chapters

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 Inc 1998 in Totowa, NJ

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 Publishers 1993 in Amsterdam