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Richard E. Wolf, Jr., Ph.D.

Professor

Richard Wolf

Office: BS 325
Phone: 410-455-2268
Email: wolf@umbc.edu

Education

Postdoctoral in Molecular Genetics, Harvard Medical School, 1975;
Ph.D. in Microbiology, University of Cincinnati, 1970
M.S. in Microbiology, University of Cincinnati, 1968
B.A. in Psychology, University of Cincinnati, 1963

Professional InterestsWolf Research

Like most faculty, my professional interests fall into three areas: research, teaching, and service. I get great pleasure from all of them. In research, I have long studied mechanisms of gene regulation in bacteria. During my initial years at UMBC, I worked on understanding growth rate-dependent regulation (GRDR) of central metabolism genes in E. coli. This form of regulation coordinates gene expression with the cellular growth rate as it is determined by the nutritional quality of the growth medium. The main gene we studied was gnd, which encodes 6-phosphogluconate dehydrogenase, an enzyme of the pentose phosphate pathway. We discovered that GRDR ofgnd is exerted at the level of translation initiation and involves the “internal complementary sequence” (ICS), a regulatory element lying deep within the gnd mRNA and whose sequence is complementary to the ribosome binding site (RBS) of the mRNA. Formation of a long-range secondary structure in the mRNA between the RBS and the ICS plays a key role in GRDR of gnd. We also studied GRDR of zwf, which encodes glucose-6-phosphate dehydrogenase.

            Studies of the GRDR  of zwf, which occurs at the level of transcription initiation, led us into our current research: the regulation of the cell’s defense against oxidative stress imposed by superoxide and mediated by SoxS, the activator of transcription of the defense response genes of which zwf is one. We also study three other proteins whose amino acid sequences are ~50% identical to that of SoxS and which activate transcription of a common set of genes, albeit to different degrees. These proteins are Rob, whose activity is induced by bile salts and dipyridyl, MarA, whose activity is induced by salicylate, a plant alarmone, and TetD, which resides in transposon Tn10 but whose inducer is unknown.
            Over the past ten years or so my primary teaching has been “Microbial Molecular Genetics”, BIOL 434/634. The course is taught almost exclusively from the original scientific literature. I don’t lecture very much. Instead, one or two papers are assigned for each two hour class period and I call on students at random to answer questions about the background, rationale, methods, data, conclusions, etc. of the papers. The general topic is mechanisms of gene regulation in E. coli. But, my philosophy for this course is that the process is more important than the content. In particular, my objective is to help students become actively involved in their own education so that when they leave the university they will be able to keep up in their chosen field by being adept at reading the relevant literature.
            In addition to classroom teaching, I get enormous pleasure from working with students in my research lab. Here my philosophy is to always be available for discussions of research problems, new directions, etc., but not to micromanage. I have been fortunate to have worked with many wonderful students and it has been extremely rewarding to have played a role in their growth as independent scientists. Sixteen students have conducted their dissertation research under my mentorship. They learned to do good science and they have gone to have interesting and productive careers.
            My main service contribution to UMBC has been in the area of new program development. Like my research and teaching, I have derived great pleasure from working to build educational programs at UMBC. Shortly after arriving at UMBC, colleagues in the Departments of Chemistry (now Chemistry and Biochemistry) and Biological Sciences and I developed a major, Biochemistry and Molecular Biology. It is a rigorous B.S. degree program and has helped to enhance UMBC’s reputation in life science research and education.
            A few years later, John Hays, my friend and colleague in the Chemistry Department, and I developed a M.S. program in Applied Molecular Biology (AMB). The purpose of the program was to train students to become middle-level researchers in the then fledgling biotechnology industry. We developed the curriculum in consultation with scientists at local biotechnology companies. We argued to UMBC administrators that this program would put UMBC on the map in molecular biology and biotechnology. They agreed and supported our initiative with four faculty positions and an up-front contribution of nearly a quarter of a million dollars for laboratory equipment. Initiation of the program was written up in The New York Times, The Wall Street Journal, and Science as the first program of its kind in the country. Now in existence for more than 25 years, the program has produced many outstanding scientists, but also some graduates have become medical doctors, veterinarians, and patent attorneys.
            Subsequently, John Hays and I proposed that UMBC develop a Ph.D. program in “Basic and Applied Molecular Biology”. This Ph.D. program was a natural extension of the AMB program and together we expected that they would help recruit outstanding graduate students to UMBC. Although the Ph.D. program was not approved by the Central Administration of the University of Maryland System, the idea was resurrected a few years later as a System-wide Ph.D. program in Molecular and Cell Biology (MOCB). Hays and I ensured that the curriculum would mesh with the AMB program, i.e., most course requirements for the MOCB program would be met by the courses of the AMB program. As a result, UMBC produced the first Ph.D. graduates of the MOCB program in the System.
            In 2006-2007, I led the development of the curriculum for a Masters in Professional Studies: Biotechnology and a Certificate in Biotechnology Management. The purpose of the program is to provide the means for working professionals in the biotechnology industry to expand their knowledge of the sciences underlying biotechnology and to learn good manufacturing practices, regulatory issues in biotechnology, as well as the tools of financial management, leadership and team building. The program, whose courses are taught exclusively in the evening at UMBC’s Tech Center, started in fall, 2007 with 14 students in the MPS program and 3 more in the Certificate program. I am the Graduate Program Director and we expect that this MPS program will be followed by others at UMBC.

Publications

Taliaferro, L.P.*, Keen*  III, E.F., Alberola-Sanchez, N. & Wolf, R.E. 2012. Transcription activation by Escherichia coli Rob at class II promoters: protein-protein interactions between Rob’s  N-terminal domain and the sigma 70 subunit of RNA polymerase. J. Mol. Biol. 419:139-157. doi:10.1016/j. jmb.2012.03.019.  *These authors contributed equally to this work.
[Abstract] [Text]

Zafar, M.A., I.M. Shah and R.E. Wolf, Jr. 2010. Protein-protein interactions between sigma 70 region 4 of RNA polymerase and Escherichia coli SoxS, a transcription activator that functions by the prerecruitment mechanism: evidence for “off-DNA” and “on-DNA” interactions”. J. Mol. Biol. 401:13-32.
[Abstract]

Griffith, K.L., M.M. Fitzpatrick and R.E. Wolf, Jr. 2009. Two functions of the C-terminal domain of Escherichia coliRob: mediating “sequestration-dispersal” as a novel off-on switch for regulating Rob’s activity as a transcription activator and preventing degradation of Rob by Lon protease. J. Mol. Biol. 388:415-430.
[Abstract]

Shah, I.M. and R. E. Wolf, Jr. 2006. Sequence requirements for Lon-dependent degradation of the Escherichia colitranscription activator SoxS: identification of the SoxS residues critical to proteolysis and specific inhibition of in vitrodegradation by a peptide comprised of the N-terminal 21 amino acid residues. J. Mol. Biol., 357:718-731.
[Abstract]

Shah, I.M. and R.E. Wolf, Jr. 2006. Inhibition of Lon-dependent degradation of the Escherichia coli transcription activator SoxS by interaction with “soxbox” DNA or RNA polymerase. Mol. Microbiol. 60:199-208.
[Abstract]

Griffith, K.L., S.M. Becker and R.E. Wolf, Jr. 2005. Characterization of TetD as a transcriptional activator of a subset of genes of the Escherichia coli SoxS/Mar/Rob regulons. Mol. Microbiol. 56:1103-1117. Erratum. Mol. Microbiol.57:306.
[Abstract]

Griffith, K.L. and R.E. Wolf, Jr. 2004. Genetic evidence for pre-recruitment as the mechanism of transcription activation by SoxS of Escherichia coli: the dominance of DNA binding mutations of SoxS. J. Mol. Biol. 344:1-10.
[Abstract]

Shah, I.M. and R.E. Wolf, Jr. 2004. Novel protein-protein interaction between Escherichia coli SoxS and the DNA binding determinant of the RNA polymerase α subunit: SoxS functions as a co-sigma factor and redeploys RNA polymerase from UP-element-containing promoters to SoxS-dependent promoters during oxidative stress. J. Mol. Biol. 343:513-532.
[Abstract]

Griffith, K .L., I.M. Shah, and R. E. Wolf, Jr. 2004. Proteolytic degradation of the Escherichia coli transcription activators SoxS and MarA as the mechanism for reversing the induction of the superoxide (SoxRS) and multiple antibiotic resistance (Mar) regulons. Mol. Microbiol. 51:1801-1816
[Abstract]

Griffith, K.L. and R.E. Wolf, Jr. (2002) A comprehensive alanine scanning mutagenesis of the Escherichia colitranscription activator SoxS: identifying amino acids important to DNA binding and transcription activation. J. Mol. Biol. 322:237-257.
[Abstract]

Griffith, K.L., I.M. Shah, T.E. Myers, M.C. O’Neill, and R.E. Wolf, Jr. (2002) Evidence for “pre-recruitment”as a new mechanism for transcription activation in Escherichia coli the large excess of SoxS binding sites per cell relative to the number of SoxS molecules per cell. Biochem. Biophys. Res. Commun. 91:979-986. Erratum. Biochem. Biophys. Res. Commun. 294:1191.
[Abstract]

Griffith, K.L. and R.E. Wolf, Jr. (2002) Measuring β-galatosidase activity in bacteria: cell growth permeabilization, and enzyme assays in 96-well arrays. Biochem. Biophys. Res. Commun. 290:397-402. Erratum. Biochem. Biophys. Res. Commun. 292:292.
[Abstract]

Griffith, K.L. and R.E. Wolf, Jr. (2001) Systematic mutagenesis of the DNA binding sites for SoxS in the Escherichia coli zwf and fpr promoters: identifying nucleotides required for DNA binding and transcription activation. Mol. Microbiol.40:1141-1154. Erratum. Mol. Microbiol. 42:571.
[Abstract]

Egan, S.M., A.J. Pease, J. Lang, X. Li, V. Rao, W.K. Gillette, R. Ruiz, J.L. Ramos, and R.E. Wolf, Jr. (2000) Transcription activation by a variety of AraC/XylS family activators does not depend on the class II-specific activation determinant in the N-terminal domain of the RNA polymerase alpha subunit. J. Bacteriol. 182:7075-7077.
[Abstract]

Wood, T.I., K.L. Griffith, W.P. Fawcett, K.-W. Jair, T.D. Schneider, and R.E. Wolf, Jr. 1999. Interdependence of the position and orientation of SoxS binding sites in the transcriptional activation of the Class I subset of Escherichia colisuperoxide-inducible promoters. Mol. Microbiol. 34:414-430.
[Abstract]

Lundberg, B.E., R.E. Wolf, Jr., M.C. Dinauer, Y.Xu, and F.C. Fang. 1999. Glucose 6-phosphate dehydrogenase is required for Salmonella typhimurium virulence and resistance to reactive oxygen and nitrogen intermediates. Infect. Immun. 67:436-438.
[Abstract]

Jair, K.-W., X.Yu, K. Skarstad, B.Thony, N. Fujita, A. Ishihama, and R. E. Wolf, Jr. 1996. Transcriptional activation of promoters of the superoxide and multiple antibiotic resistance regulons by Rob, a binding protein of the Escherichia coli origin of chromosomal replication. J. Bacteriol., 178:2507-2513.
[Abstract]

Martin, R.G., K.-W. Jair, R.E. Wolf, Jr., and J.L. Rosner. 1996. Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli. J. Bacteriol.:178:2216-2223.
[Abstract]

Jair, K.W., W.P. Fawcett, N. Fujita, A. Ishihama, and R.E. Wolf, Jr. 1996. Amibdextrous transcriptional activation by SoxS: Requirement for the C-terminal domain of the RNA polymerasae alpha subunit in a subset of Escherichia colisuperoxide inducible genes. Mol. Microbiol., 19:307-317.
[Abstract]

Jair, K.-W., R.G. Martin, J.L. Rosner, N. Fujita, A. Ishihama, andR.E. Wolf, Jr. 1995. Purification and regulatory properties of MarA protein, a transcriptional activator of Escherichia coli multiple antibiotic resistance and superoxide resistance promoters. J. Bacteriol.177:7100- 7104.
[Abstract]

Fawcett, W.P., and R.E. Wolf, Jr. 1995. Genetic definition of the Escherichia coli zwf”soxbox”, the DNA binding site for SoxS-mediated induction of glucose 6-phosphate dehydrogenase in response to superoxide. J. Bacteriol.177:1742-1750.
[Abstract]

Chang, J.T. C. B.-R. Green, and R.E. Wolf, Jr. 1995. Inhibition of translation initiation on Escherichia coli gnd mRNA by formation of a long range secondary structure involving the ribosome binding site and the internal complementary sequence. J. Bacteriol.177:6560-6567.
[Abstract]

Fawcett, W.P., and R.E. Wolf, Jr. 1994. Purification of a MalE-SoxS fusion protein and identification of the control sites of Escherichia coli superoxide-inducible genes. Mol. Microbiol. 14:669-679.
[Abstract]

Courses Taught

BIOL 434: Microbial Molecular Genetics
BIOL 634: Microbial Molecular Genetics
BIOL 739: Research Seminar in Molecular Biology
BIOL 899: Doctoral Dissertation Research
BIOL 602: Introduction to Laboratory/Field Research
BIOL 101: Concepts of Biology
BIOL 275: Microbiology
BIOL 302: Molecular and General Genetics
BIOL 710: Graduate Seminar: Topics in Genetics
APMB 798: Research in Applied Molecular Biology
BIOL 799: Masters Thesis Research