Keifer Lab

Joyce Keifer, Ph.D.


Neuroscience Group

Division of Basic Biomedical Sciences

University of South Dakota

Sanford School of Medicine

Vermillion, SD  57069-2390

  tel:   (605)  658-6355

  fax:  (605)  677-6381




Ph.D. in Neuroscience,  University of Wisconsin - Madison, 1987     

B.S. in Physiological Psychology, Arizona State University, 1980



Northwestern University Medical School, Department of Physiology, 1987 - 1991

Professor, University of South Dakota Sanford School of Medicine; Division of Basic Biomedical Sciences, 2003 - present

DirectorNIH COBRE on Neural Mechanisms of Adaptive Behavior, USD, 2000 - 2011

Associate Professor, University of South Dakota School of Medicine; Division of Basic Biomedical Sciences, 1997 - 2003

Assistant Professor, University of South Dakota School of Medicine; Department of Anatomy and Structural Biology, 1993 - 1997

Research Assistant Professor, Northwestern University Medical School; Department of Physiology, 1991—1993


Research Interests

Learning and memory requires rapid and coordinated gene expression in response to specific environmental stimuli. To elucidate the epigenetic mechanisms that regulate activity-dependent gene expression and alternative splicing, our laboratory utilizes a neural correlate of eyeblink classical conditioning using an ex vivo brainstem preparation from the turtle brain. Paired stimulation of the cranial nerves evokes a behavioral, albeit “fictive”, physiological response that mimics conditioning in behaving animals. Major projects in our lab include analysis of activity-dependent epigenetic regulation of plasticity genes in response to sensory nerve stimulation during conditioning. Here, we are examining the hypothesis that plasticity and immediate early genes (IEGs) such as the brain-derived neurotrophic factor (BDNF) gene are uniquely ‘poised’ by histone modifications for rapid transcriptional activation or repression in response to environmental stimuli (Keifer, 2017, in Genes; PMID28208656).

In a second project, mechanisms that regulate learning-dependent alternative splicing of the BDNF gene by the methyl-CpG-binding protein 2 (MeCP2), which is implicated in the neurodevelopmental disorder Rett syndrome, is under study. Here, we have observed that loss of MeCP2 function surprisingly inhibits Tet1 BDNF binding, thereby negatively impacting DNA methylation and splicing regulation (Zheng et al., 2017, in eLife; PMID28594324).

These studies will detail mechanisms underlying the rapid regulation of gene expression and alternative splicing during normal learning and synaptic plasticity. Moreover, they will provide insight into mechanisms for misregulation of gene expression in disease states such as Alzheimer’s dementia and Rett syndrome, and contribute to findings aimed at determining whether features of the epigenetic architecture will prove useful for early detection of cognitive disorders and dementia.