Education

Degree	Institution	Major
BS	Loyola University	Biology
MPhil	Yale University	Human Genetics
PhD	Yale University	Human Genetics

Post-Graduate Training

Training	Institution	Specialty
Postdoctoral	University of Colorado	Genetic organization of hypotrichous ciliated protozoa in the laboratory of Dr. D. M. Prescott

Awards

Name of Award/Honor	Awarding Organization
Who’s Who in America	Who's Who Amoung Students in Amerian Universities
“Superior” rating	Medical School Teaching Assessment Program
Postdoctoral Fellowship (declined).	Anna Fuller Fund
National Institutes of Health Postdoctoral Fellowship, 1980-83.	NIH
Hudson Award for summer study	Loyola University
Member 1973-1974	Blue Key National Honor Fraternity
Biology Medal	Loyola University
Illinois State Scholar, 1970-1974.	Illinois Student Assistance Commission

Name & Description	Category	Role	Type	Scope	Start Year	End Year
Advisory Committee; Moore Foundation Dinoflagellate Transformation Project (PI, Dr. Senjie Lin, UCONN, Storrs)	Advisory Committee	member	UConn-Storrs	National	2018	2018
Medical School Dean's Predatory Journal and Conference Task Force	Research Committee	member	UConn Health	University	2018	2019
UCONN Research Excellence Program (REP) Stimulus Grant Review Committee	Research Committee	member	Other	University	2018	2018
UCH Graduate School Mentorship and Leadership Awards Committee	Advisory Committee	member	UConn Health	University	2017	2018
Farmington Public Schools Foundation	Advisory Committee	Board of Directors	External	Local	2010	2013
Student Evaluation and Appeal Review Committee (SEARC; Medical & Dental students)	Advisory Committee	Member	Other	University	2009
LCME Institutional Setting Self-Study Committee	Advisory Committee	Co-Chair	UConn Health	University	2008	2010
Education Council	Education Committee	Member	UConn Health	University	2007	2011
Executive Committee of the Graduate Faculty Council	Advisory Committee	Member	UConn Health	University	2007	2018
Eukaryotic Cell	Editorial Board	Board of Reviewers	External	National	2006
Medical School Oversight Committee	Education Committee	Vice Chair	UConn Health	University	2006	2007
Education Council Subcommittee on Evaluation of Teaching	Education Committee	Member	UConn Health	University	2006	2006
Nominating Committee, International Society of Protistologists	Professional/Scientific Organization	Member	External	National	2006	2007
The American Society for Cell Biology	Professional/Scientific Organization	Member	External	National	2005	2015
American Society for Microbiology	Professional/Scientific Organization	Member	External	National	2005
American Society for Cell Biology	Professional/Scientific Organization	Member	External	National	2005
Medical Council Subcommittee on Tenure and Salary	Advisory Committee	Co-Chair	UConn Health	University	2004	2005
Graduate Programs Strategic Planning Committee	Education Committee	Member	UConn Health	University	2004	2005
FASEB Summer Research Conference on “Ciliate Molecular Biology”	Professional/Scientific Organization	Co-Chair	External	National	2003
Board of Scientific Advisors, joint NIGMS/NSF-funded Tetrahymena Genome-Sequencing Project	Advisory Committee	Member	External	National	2003	2006
Medical Council Subcommittee on Post-Tenure Review	Advisory Committee	Member	UConn Health	University	2003
Medical School Council, Executive Committee	Education Committee	Member	UConn Health	University	2003	2005
Tetrahymena Genome Sequencing Steering Committee	Advisory Committee	Steering Committee	External	National	2001	2007
Journal of Eukaryotic Microbiology	Editorial Board	Associate Editor	External	National	2000	2008
UCONN Medical School Senior Appointments and Promotions Committee	Advisory Committee	Member	UConn Health	University	2000	2007
Curriculum Committee, Graduate Program in Molecular Biology and Biochemistry	Education Committee	Chair	UConn Health	University	1999	2000
Medical School Council	Education Committee	Member	UConn Health	University	1997	2005
Journal of Protozoology/Journal of Eukaryotic Microbiology	Editorial Board	Reviewer	External	National	1997	2000
Medical Council Nominating Committee	Advisory Committee	Chairman	UConn Health	University	1995
U. Conn. Health Center Graduate Programs Committee	Advisory Committee	Vice Chair	UConn Health	University	1995	1996
UCONN Graduate School task force on Area Review Committees	Advisory Committee	Member	UConn Health	University	1995	1996
Advisory Panel for Eukaryotic Genetics, National Science Foundation, 1993-96, 2001.	Advisory Committee	Panel member	External	National	1993
Graduate Faculty Council and Executive Committee	Advisory Committee	Member	UConn Health	University	1993	1995
Board of Reviewers,97-00.	Advisory Committee	Member	External	National	1992	1995
University of Connecticut Health Center Graduate Programs Committee	Education Committee	Chairman	UConn Health	University	1992	1995
Univ. of Conn. Health Center Strategic Planning/Research Focus Committee	Research Committee	Member	UConn Health	University	1992
Dental School Council, 1984-89	Advisory Committee	Member	UConn Health	University	1991	1993
Univ. of Conn. Health Center Oversight Committee on Research (OCOR)	Research Committee	Member	UConn Health	University	1991	1993
Dental School Council	Education Committee	Member	UConn Health	University	1991	1993
Friends of Farmington Education	Professional/Scientific Organization	Member	External	Local	1990	1991
Gordon Conference on "The Molecular Biology of Ciliated Protozoa"	Professional/Scientific Organization	Co-Chair	External	National	1989
Graduate Program in Molecular Biology and Biochemistry	Education Committee	Director	UConn Health	University	1989	1992
Graduate Programs’ “Undergraduate Symposia on Current Topics in the Biological and Biomedical Sciences	Other	Co- Chair	UConn Health	University	1989
Journal of Protozoology/Journal of Eukaryotic Microbiology	Editorial Board	Reviewer	External	National	1989	1995
Committee on Research Safety & Environmental Health	Advisory Committee	Vice Chair	UConn Health	University	1988	1989
University of Connecticut Research Foundation Institutional Grant Review, Basic Sciences	Advisory Committee	Member	UConn Health	University	1987	1990
Graduate Program in Molecular Biology and Biochemistry	Education Committee	Assistant Director	UConn Health	University	1987	1989
Graduate Programs’ “Undergraduate Symposia on Current Topics in the Biological and Biomedical Sciences	Other	Chairman	UConn Health	University	1987
Society of Protozoologists	Professional/Scientific Organization	Member	External	National	1986
Admissions Committee, Graduate Program in Molecular Biology and Biochemistry	Advisory Committee	Member	UConn Health	University	1986	1995
Curriculum Revision Committee, Graduate Program in Molecular Biology and Biochemistry	Education Committee	Member	UConn Health	University	1985	1986
American Cancer Society Institutional Grant Review Committee	Study Section	Grant Reviewer	UConn Health	University	1984	1987
Medical School Applicant Interviews	Advisory Committee	Member	UConn Health	University	1984	1986
Dental School Council	Education Committee	Member	UConn Health	University	1984	1989
Society of Protozoologists	Professional/Scientific Organization	member	External	International	1984
Sigma Xi, Scientific Research Society	Professional/Scientific Organization	Member	External	National	1980
American Association for the Advancement of Science	Professional/Scientific Organization	Member	External	National	1978
American Association for the Advancement of Science	Professional/Scientific Organization	member	External	National

The laboratory employs ciliated protozoa as model organisms to study basic cellular processes. Currently, the following two areas of research are being pursued:

Phagocytosis in Tetrahymena thermophila.
Phagocytosis refers to the process by which cells are able to ingest large particles (>1 um). In vertebrates, phagocytosis mainly occurs in specialized cells of the immune system (macrophages, monocyctes, and neutrophils). Such “professional phagocytes” serve as a primary line of defense by ingesting invading pathogens, and also activate specific immune responses. In addition, phagocytosis is important in clearing cell debris and for tissue remodeling during development. Finally, a number of microbial pathogens (e.g., Salmonella, Legionella, Mycobacterium, anthrax, and specific types of yeast) utilize and/or subvert phagocytosis as a means of entering cells. Learning how phagocytosis is carried out is thus important for understanding tissue maintenance and immune defense in humans, as well as the infection strategies of some disease-causing microorganisms.

Research in a number of experimental systems has made it clear that phagocytosis is a multistep process that involves hundreds of genes and proteins. Nonetheless, the identities and functions of phagocytic genes, and the molecular mechanisms of phagocytosis, are still poorly understood. We are seeking to further our understanding of phagocytosis by studying Tetrahymena thermophila, an organisms particularly amenable to genetic and molecular biological analysis. In nature, Tetrahymena uses phagocytosis to feed on bacteria and other microorganisms, but in the laboratory it can be grown on defined culture medium where phagocytosis is not an essential process. This feature has allowed us to develop a screening procedure for isolating cells that are deficient in phagocytosis, which will lead to the identification of new genes/proteins that are involved in various steps of the process. In addition, a system for the efficient purification of phagosomes from Tetrahymena has been developed, and we are pursuing mass spectrometry approaches to define the complete Tetrahymena phagosome proteome. This analysis is expected to identify numerous new genes previously unsuspected of playing a role in phagocytosis. The genetic tools available in Tetrahymena, coupled with its favorable cytological features, will allow us to investigate the localization and function of these novel proteins.

Frequent Frameshifting in Euplotes crassus.
Ciliated protozoa, including members of the genus Euplotes, are unusual in that they employ alternative genetic codes to specify how mRNAs are translated into proteins. Previously. the genetic code had been considered universal and unalterable. The observation that many ciliates have altered genetic codes in which canonical stop codons are decoded as sense (stop codon reassignment) shows that even the code is subject to evolutionary pressure to change. In addition, recent data suggest that Euplotes genes also have an unusually high frequency of programmed +1 translational frameshifting. In our own pilot sequencing survey of 25 randomly selected genes, we observed 3 genes that require a +1 frameshift, indicating that more than 10% of the genes in the genome may require such a frameshift for expression. we have also carried out a phylogenetic analysis on the origin of frameshift sites within the telomerase reverse transcriptase genes of Euplotes species, and have found that two frameshift sites have arisen during the evolution of this group. In other organisms, frameshifting is involved in regulation of gene expression. The apparent high frequency of frameshift genes in Euplotes is unprecedented, and suggests that the organism has particular features that have potentiated the origin of frameshift sites within genes and that allow for efficient frameshifting.

The mechanism of frameshifting in Euplotes is unknown. The initial open reading frame of all the Euplotes frameshift genes terminates with an AAA lysine codon, followed by a stop codon (usually UAA), and an additional A residue. This AAA-UAA-A motif suggests that the Euplotes genes may employ a "shifty stop" mode of frameshifting. There are two features of a typical "shifty stop" site. First, there is a slippery codon (AAA in Euplotes) that, during translation, would allow the cognate tRNA to slip forward 1 base and still maintain two correct base pairs with the mRNA. Second, there is a poorly recognized termination tetranucleotide (the stop codon plus the next base) that is thought to slow translation, providing an opportunity for the usually rare slippage in reading frame. Surprisingly, and perhaps contrary to this model, UAA-A frequently occurs at natural sites of translation termination in Euplotes. To explain this apparent enigma, we have developed a model in which stop codon reassignment is linked to the mechanism of frameshifting (Klobutcher and Farabaugh, 2002, Cell 111:763). Stop codon reassignment requires changes in the translation termination factor eRF1 such that it can no longer recognize the reassigned stop codon (UGA in Euplotes). We postulate that these changes have also impaired the recognition of the remaining stop codons, so that translation termination is a slow step. Thus, the slowing of translation when a stop codon is encountered would provide an opportunity for a +1 frameshift in the context of a slippery codon. We plan to test this model by both defining the minimal nucleic acid sequence element(s) that promotes frameshifting, and by determining if Euplotes eRF1 has reduced affinity for stop codons. As a further test of the hypothesis, we plan to determine if a high frequency of frameshifting is observed in other ciliates that have independently undergone stop codon reassignment.

Not accepting students for Lab Rotations at this time

Journal Articles

Book Chapters

Abstracts

Other

Reviews

Short Surveys