Winter 2002/2003 Newsletter

It is my sad duty to inform you that Carl O. Clagett, Professor Emeritus of Biochemistry, passed away on June 8, 2002 at the age of 89. He received a B.S. in biochemistry in 1939 from Penn State, a M.S. in 1941 and a Ph.D. in biochemistry in 1947, both from the University of Wisconsin. He served as head of the Experiment Station at North Dakota State University from 1947-1956. From 1956 until his retirement in 1978, he was professor of biochemistry at Penn State. In 1982, he received the Eberly College of Science Distinguished Alumni Award. In his memory, contributions may be sent to the Biochemistry and Molecular Biology Department. Contributions should be sent to 430 Thomas Building, University Park, PA 15802.

Although Joe does not study heart-muscle genes directly, his model system a regulatory protein in yeast that functions like heart-muscle-specific factors ha s enabled him to understand gene expression. He has determined that a specific protein controls the expression of the genes, and that the same protein either facilitates or prevents that expression. A better understanding of the mechanism related to the regulation of this gene would provide a valuable resource for research related to cardiac health.

"We are using a model system to study how proteins that regulate gene expression can function as a repressor under one circumstance and an activator under another. Understanding the mechanism of how these genes are controlled and what causes the switch from the repressed to the activated state is critical toward developing drugs and therapies aimed at augmenting the repair of damaged tissue."

Prior to joining the faculty at Penn State in 1997, Joe conducted postdoctoral research at the University of Massachusetts Medical Center and at the University of Illinois. He earned his doctoral and masters degrees, both in molecular physiology, at the University of Illinois in 1992 and 1990, respectively. He earned his bachelor's degree in biology, with a chemistry minor, at Boston University in 1988.

Research in Craig's laboratory focuses on positive-strand RNA viruses, which cause diseases ranging from the common cold to chronic hepatitis. While infection by some of those viruses can be stopped by the immune system alone or with the help of vaccinations, other similar viruses change so quickly that neither approach works. "Currently, there is no effective therapy for viruses that change so rapidly. The long-term goal of our laboratory is to define the molecular mechanism of RNA-virus genome replication with the hope of using this information to design strategies to treat diseases caused by this class of viruses."

Cameron completed his postdoctoral work at Penn State in 1997 after earning his doctoral degree in biochemistry at Case Western Reserve University in 1993. He earned his bachelor's degree, magna cum laude in chemistry at Howard University in 1987. He was named to the Louis Martarano Career Development Professorship in 2002.

A few years ago, we began having a reception in the spring to honor our undergraduates, graduate students and postdocs who received national recognition in the preceding year. In addition, we inscribe their names and their awards on plaques in 456 N. Frear where the receptions are held. Last year's recipients were:

Other award recipients whose names have been inscribed on the several plaques in the Althouse lobby include:

Anthony Grippe (Booker) - Frederick C. Wedler Outstanding Honors Dissertation Award
Michael Fetchko (Lai) - Frederick C. Wedler Outstanding Doctoral Dissertation Award
Song Tan - Tershak Outstanding Faculty Teaching Award
Gregory Grove - Althouse Outstanding Instructor Teaching Award
David Iwig (Booker) - Althouse Outstanding Teaching Assistant

Dr. Thomas Silhavy presented the Stone Lecture in Microbiology, titled "Coping with External Stress." Dr. Silhavy is Professor of Molecular Biology at Princeton University.

Dr. Jonathan Widom presented the Pollard Lecture in Biophysics or Molecular Biology, titled "Chromosome Structure and Gene Regulation." Dr. Widom is Professor of Chemistry at Northwestern University.

Xenobiotic Receptors in Toxicology and Carcinogenesis was the topic of the 21^st Penn State Summer Symposium in Molecular Biology held July 31-August 3, 2002. Ron Evans, from the Salk Institute, gave a keynote address, "Nuclear Receptors and the Exotics of Xenobiotics."

One of the first projects of the committee was to organize a series of “laboratory open houses” to help the members of the department to get to know each other better. Every other Friday afternoon one floor in Althouse Laboratory or North / South Frear Laboratories welcomed the rest of the department with research displays and good food.

Dean Larson also has asked the committees to develop plans to improve the look and feel of the primary place(s) in the department where we interact with students. We are focusing on creating a respectful, multi-culturally welcoming environment, with attention not only to the physical characteristics of the space, but also the quality of service and support among the individuals interacting in these places.

The committee is composed of seven members representing various constituencies within the department: Andrea Mastro, chair (senior faculty), Craig Cameron (junior faculty), Ole Sodiende (instructors), Carol Baker (research personnel), Joyce Greslick (staff), David Iwig (graduate students) and Marci Laudenslager (undergraduate students). Drs. Mastro and Cameron previously served on the College Climate and Diversity Committee; Drs. Sodiende and Baker are current members of the College Committee.

The committee welcomes comments and suggestions from present and former students as to how we can improve the working climate for all.

Impossible Vaccine Tames Staphylococcus aureus
A vaccine they said couldn’t be done points the way to controlling antibiotic-resistant, hospital-acquired infections.
By Tom Hollon
Reprinted with permission from The Scientist, July 8, 2002

If Scottish surgeon Alexander Ogsten ever daydreamed that discovering Staphylococcus aureus would win acclamation, it was before he crossed paths with the British Medical Journal and came away the worse for it, squashed like a cockroach caught currying across a tray of tea and crumpets. Upbraiding the upstart for daring to step beyond his place, the editor dismissed Ogsten’s 1881 paper on the bacterium, jotting in swift strokes of ink that “little of any work comes from Scotland.”

Let us pause a moment to savor this naked insult, those of us who admit to guilty pleasure in watching scientists fight, for here the curtains opened upon a field in which interesting acrimony has often flourished right alongside interesting science. Credit this state of delight to the molecular properties of S. aureus, being as it is somewhat different from those of its brethren, and so a continual source of disagreement and rancor. S. aureus does not welcome the faint of heart or thin-skinned.

With this as background, it is understandable that some observers of the field may have found a double meaning in recent news from the New England Journal of Medicine¹ that a polysaccharide-based vaccine protects patients undergoing hemodialysis from S. aureus infection. It was, of course, a fine achievement for medicine. But in some corners there may have been a tinge of the bittersweet in knowing that a dispute over whether a staph vaccine was even possible, a dispute that more than once erupted in bouts of sputtering range between opposing researchers, was at last being laid to rest. Who would have guessed when it began that the controversy would last the better part of 30 years.

The fight was over polysaccharides: Did S. aureus have them? Could they be used for a vaccine? Year after year, the weight of the data said no. That the truth turned out otherwise that it was found at all “comes down to the persistence of a small group of people,” says Ali Fattom, who directed research on the vaccine at the Rockville, Md., laboratories of Nabi Biopharmaceuticals. He ought to know, as a battle-scarred defender of a vaccine few thought would every work.

A coat of a different color, Staphylococcus aureus is a Gram-positive bacterium found in several types of farm animals, but the privilege of being its chief reservoir belongs to humans; one in four people offers it home and shelter on skin and nasal passages. (Streaked on agar plates, its colonies are intensely yellow, hence the Latin aureus.) Mostly its presence is of no concern. But in some neonates, immuno-suppressed patients, patients undergoing surgery it can cause serious infections including pneumonia, osteomyelitis, endocarditis, toxic shock syndrome, and sepsis, and it can be lethal.

Often these infections occur in hospitals. Nearly a quarter of nonsocomial, or hospital-acquired, infections are due to S. aureus. And increasingly, they are antibiotic-resistant. Half of hospital-isolated S. aureus strains resist methicillin, the preferred treatment, and since 1997 physicians have watched with alarm as strains emerged resistant to vancomycin, the only antibiotic that works when methicillin does not.

In the 1950s and 1960s it became apparent that for some pathogens, polysaccharide-based vaccines offered alternatives to antibiotics. Polysaccharides are the major components of the outer layer, or capsule, of bacteria. Polysaccharides are poor antigens, and for this reason capsules increase bacterial resistance to antibody-mediated ingestion (opsonization) and destruction (phagocytosis) by macrophages and other immune cell scavengers. Nevertheless, even poor antigens can be turned to medical purpose; vaccinologists found that killed whole bacteria and large does of purified polysaccharides sometimes produced antipolysaccharide antibodies capable of protecting against infection.

Capsules are associated with Gram-positive bacteria, so it seemed reasonable that the capsular polysaccharides of S. aureus might serve as the basis for a vaccine. But the idea was not long-lived, as intensive efforts to find its polysaccharides failed. By the mid-60s researchers drew the logical conclusion S. aureus did not have polysaccharides and vaccine efforts halted.

“You’re wasting your time.” Here matters might have rested, with never a harsh word spoken, had not Walter Karakawa, heedless of all better judgment, resumed the polysaccharide hunt in 1974. Karakawa noticed that the earlier investigations used laboratory strains of S. aureus, not organisms cultured from infectious isolates. S. aureus polysaccharides were undetectable by the standard methods (microscopy with India ink staining; morphological studies of bacterial colonies with and without polysaccharides), so Karakawa pinned his hopes on a serological approach. Beginning at Pennsylvania State University, Karakawa collected antisera from animals injected with S. aureus obtained from clinical isolates. By painstakingly tabulating how many isolates each antisera preparation recognized, over the course of 15 years he discovered eight capsular types, of which types 5 and 8 accounted for 85% of infections.

There was punishment, though, for researching a settled question: Karakawa was denied grant funding for his work. What kept him going was a patron: The eminent vaccinologist John B. Robbins of the National Institutes of Health took Karakawa under his wing. Robbins has worked on the first Pneumococcus vaccine, the first Meningococcus vaccine, and the first Hemophilus influenza B vaccine, and in the early 1980s was pioneering conjugate vaccines, which transform weak polysaccharide antigens into antigens of power. With Karakawa’s help, Robbins intended to buck consensus opinion and add a conjugate Staphylococcus aureus vaccine to his string of successes.

A conjugate vaccine links a capsular polysaccharide to a carrier protein in order to trick helper T cells into recognizing polysaccharides as antigens, not something they would otherwise do. When the antigen-presenting calls process the carrier protein for T-cell recognition, the attached polysaccharide necessarily gets the same treatment. While B cells do not require the help from T cells to produce antipolysaccharide antibodies, stimulation by T helper cells activated by polysaccharide antigens makes all the difference antibodies with dramatically higher affinity are produced, as well as surging titers in instances of reinfection.

Antibodies against capsule types 5 and 8 were not crossprotective, so an effective vaccine required a component for each type, separately tested for safety and immunogenicity, then combined and tested for efficacy. The project began in earnest in 1986, when Fattom, arriving in Robbin’s lab fresh from his doctoral work at Hebrew University on microbial life in the Dead Sea, was assigned the job of making the vaccine.

Fattom gradually realized that with his responsibility and rising seniority came unsought status as a lightning rod for criticism leveled at the vaccine. Increasingly he would be the one to defend it in what he refers to as “hot discussions” at meetings. At that time, most researchers conceded that Karakawa had proven the polysaccharides existed; the chemical structures had been worked out, the various chemical properties explained the failure of the India ink and colony morphology studies. But the concession did not extend to the existence of capsules. Rather, S. aureus became known for its microcapsules, small patches of polysaccharide coating discernable only with an electron microscope. Whether microcapsule polysaccharides could be used for a vaccine was debatable.

By 1990, types 5 and 8 vaccines were ready for safety testing in humans. Fattom had attached the polysaccharides to a nontoxic, recombinant carrier protein derived from Pseudomonas aeruginosa exoprotein A. Also around that time, he left NIH for Univax Biologics, of Rockville, Md. (since acquired by Nabi, of Boca Raton, Fla.), to work on vaccine manufacture and clinical testing.

When Univax announced three years later that Phase I trials showed both vaccines were safe and elicited type-specific antibodies in humans, the academic community responded pretty much as always unenthusiastically. Fattom was still the go-nowhere guy with the go-nowhere vaccine, although now for a different reason. “Ok, so you have antibodies,” is the typical comment he remembers. “They won’t protect against infection.” That view was based on failure of animal experiments to prove antibodies against types 5 and 8 prevented S. aureus infections from being lethal. Evidence from humans seemed to indicate the same thing: In the course of the safety trials it was discovered that practically everyone has antibodies against type 5 and 8, simply because of normal environmental exposure, and clearly those antibodies do not protect against bacteremia.

Although Fattom recalls widespread support at Univax, he was not working in a cloister. Choruses of “You’re wasting your time” were reaching the ears of company president Thomas Stagnero, forcing him to decide whether to keep the project or kill it. “He could easily have said, ‘Let’s drop it.’” Recalls Fattom. Had Stagnero been a scientist rather than a businessman, he might have done just that. Instead, he expressed confidence that Karakawa, Robbins, and Fattom were on the right track and told them to press ahead.

This brush with termination marked a turning point, for it convinced Fattom that he needed to demonstrate with an animal model that antibodies against polysaccharides protected against infection. This had not been done earlier because the NIH and Univax researchers did not develop an animal model. Robbins’ goal had been to get the vaccine into the clinic quickly and safely, not to research the molecular basis of virulence. So animal model development had been deferred.

With his own animal model Fattom could address what he saw as flaws in other researchers’ experiments. As a postdoc, he had discovered that culture conditions made the difference between capsules and microcapsules, and many previous studies used poor culture conditions. Polysaccharide production peaks in late logarithmic and stationary growth phases after the point at which most researchers harvest bacteria. And, commonly used broths containing too much phosphate, reducing polysaccharide production; decrease the phosphate level to that of blood, and polysaccharide production soars. Fattom faulted other experiments for testing low-potency, whole-cell vaccines, or for challenging animals with huge inoculums that overwhelmed the immune response. The naturally acquired antitype 5 and 8 antibodies were low-titer, low-affinity products of B cells unstimulated by T cells. Titers of so-called T cell-independent antibodies do not reach high titers upon reinfection, which is why surgery can result in S. aureus bacteremia surgical wounds can allow in enough bacteria to overwhelm low-level antibody protection.

In 1996 Fattom finally developed a mouse model in which a reasonable innoculum caused infection. With this model he was the first to demonstrate that conjugate vaccines protected against lethal injections of Staphylococcus aureus. Knowing he would need corroboration, he then invited Jean C. Lee of Harvard to test his vaccines in her endocarditis model with rats. A year later the results were just as he predicted the vaccines protected Lee’s rats.² Now, at last, skeptics started to come around. Maybe the vaccine would work.

The trial. The randomized, double-blind clinical trial reported in the New England Journal of Medicine tested the efficacy of StaphVax, the combined types 5 and 8 conjugate vaccine, in patients on hemodialysis due to end-stage renal failure. It is a group “notorious for S. aureus bacteremia.” Says Fattom; using dialysis equipment several times a week greatly heightens the risk of bacteria entering through breaks in the skin.

The clinical trial demonstrated that between three and 40 weeks, S. aureus bacteremia developed in 11 of 892 vaccinated patients and 26 of 906 control patients. The lower rate of infection in the vaccinated group was statistically significant, indicating an estimated vaccination efficacy of 57%. Even so, protection disappeared after 10 months due to unexpected declines in antibody titers by one-half in only six months. (In healthy people the drop would have been 10-15%.) In hindsight, the decline might have been foreseen, Fattom says. Between dialysis treatments uremia develops, and high uric acid levels impair white-cell impairment. And, they were old (median age, 59). Unless white blood cells stay in good shape, he says, “antibodies are not efficient in protecting you.”

Eventually, another major market for the vaccine will be patients scheduled for surgery, people whose white blood cells are usually healthy. If StaphVax administered two weeks before surgery prevents S. aureus bacteremia (a 1-4% risk), the vaccine will likely be offered to millions of people each year. Arguably Nabi could control a billion-dollar market, with no competitor; belief that the vaccine was impossible was so strong that no other company tried to make one.

The vaccine remains a few years away from the market; the Food and Drug Administration has requested that Nabi repeat the trial before asking for market approval. Although something could always go wrong next time, the weight of opinion now is that the vaccine is going to make it.

Fattom has been touched by the many congratulations he has received from colleagues and their comments on how much the vaccine is needed. He feels vindicated. But he is also the survivor of an ordeal: “I am today a different man than the one who started this whole thing,” he says, “getting into fights.” He knows the battles were about data, not personalities. It was because he believed in his data that he kept pushing. “If you believe in something,” he says, “and you have the scientific basis to move things forward, there’s always a chance for you to do it.” Ogsten would undoubtedly agree. After all, one way or another, doesn’t almost everything of any worth come from Scotland?

¹H. Shinefield et al., “Use of a Staphylococcus aureus conjugate vaccine in patients receiving hemodialysis,” New England Journal of Medicine, 346: 491-6, Feb 14, 2002.

²J.C. Lee et al., “Protective efficacy of antibodies to the Staphylococcus aureus type 5 capsular polysaccharide in a modified model of endocarditis in rats.” Infection and Immunity, 65: 4146-51, 1997.

Of the three domains in which living things are classified, the Archaea domain is likely the least familiar to most people--but Ferry and his research team aim to make it much more well known to scientists by revealing many of its secrets. Unlike organisms in the other two domains--the Bacteria and the Eucarya, which include plants, animals, fungi, algae, and other familiar organisms--the Archaea domain includes exotic forms of bacteria that live in extreme environments such as hot springs and salt lakes.

"Our efforts are expected to greatly expand the knowledge of novel biochemical and molecular biological characteristics of the Archaea, some of which are totally unique while others are a blend that appears to be 'borrowed' from both the Bacteria and Eucarya," Ferry says. The consortium's results are expected to contribute to a fundamental understanding of the Bacteria and Eucarya domains, as well.

The consortium is a collaborative research effort led by Penn State that includes researchers at the Whitehead/Massachusetts Institute of Technology Institute for Genomic Research, the University of California at Los Angeles (UCLA), and the University of Maryland Center for Marine Biotechnology.

The model organism chosen for the project was first discovered by Ferry's laboratory living in oxygen-starved marine sediments from the Scripps canyon near La Jolla Shores in California. This species, named Methanosarcina acetivorans, ranks as the most metabolically diverse of all the Archaea because it has the largest genome yet sequenced from an Archaea organism--4.5 million base pairs.

"Our basic approach is to exploit this genomic sequence through the use of DNA microarrays to identify the genes that are regulated in response to environmental changes," Ferry explains. Researchers in the consortium also plan to supplement this approach with genetic and bioinformatic techniques used in genomics research and with enzyme techniques used in proteomics research. The consortium's research on proteins is an outgrowth of the NSF-funded Penn State Center for Microbial Structural Biology, which Ferry also directs. Daniel Jones, a senior scientist and the director of the Penn State Mass Spectroscopy Facility, will assist consortium researchers in their studies of cellular proteins with the analysis of two-dimensional gel-electrophoresis patterns.

"By exploring the metabolic diversity of our model organism we hope to discover novel enzymes and proteins with potential uses in biotechnology," Ferry says. The consortium's model organism and others like it, which produce methane, are ancient microbes whose direct ancestors are thought to have evolved at the time of the origin of life. "One expected outcome of the project is a more thorough understanding of the origin and early evolution of life--a goal that dovetails with those of the Penn State Center for Astrobiology, of which our lab is a member," Ferry comments. "In addition, anaerobic microbial food chains are essential links in the global carbon cycle, annually producing nearly a billion tons of methane--a potent greenhouse gas--so a better understanding of this process will have global environmental significance."

The bacterium, named Chlorobium tepidum, originally was discovered in New Zealand living in sulfur-rich, oxygen-depleted hot springs. "C. tepidum has a single chromosome that contains almost 2.2 million base pairs encoding a total of 2,288 genes," Bryant explains. The genes involved in photosynthesis are of particular interest to scientists studying the evolution of plants because members of the phylum Chlorobia perform photosynthesis without evolving oxygen, a trait that sets them apart from the more familiar plants and cyanobacteria--organisms to which Chlorobia are not closely related. "All Chlorobia are adapted to perform photosynthesis in very-low-light environments and form unique light-harvesting structures called chlorosomes, each of which can contain up to 250,000 chlorophyll molecules," Bryant says. The light energy harvested by chlorosomes is efficiently transferred to reaction centers that distantly resemble one of the two types found in plants and cyanobacteria. Chlorobia are also among the few organisms that oxidize sulfur compounds while converting carbon dioxide from the atmosphere into energy-rich biomolecules. "The results of this study may help to elucidate the evolution of photosynthesis, to define new biochemical pathways for energy production, and to understand better the global cycling of sulfur, nitrogen, and carbon by microorganisms," Bryant says.

Researchers Identify Protein Important for Beginning Gene-Activation Process
by Steve Sampsell, Eberly College of Science Staff Writer

Researchers at Penn State have identified the single protein that initiates the gene-activation process in yeast when it marks the start of a gene and allows the transcription process to begin. An important step toward a better understanding of the gene-activation process, the discovery also promises potential applications in the effort to combat diseases such as cancer and leukemia because a comparable protein exists in humans.

The research findings were published in the 22 June 2001 edition of Science.

"We had known that proteins were attracted to the end of a gene in order to start the process, but the question was which protein did the work," says Jerry Workman, the Paul Berg Professor of Biochemistry at Penn State and an associate investigator with the Howard Hughes Medical Institute. "What we found was an interesting protein, Tra1, that has a human homolog, Trrap, which has been implicated as an important factor in the transformation of cells into cancer cells by several oncogene products, proteins that are active in a number of tumors."

Using an interdisciplinary approach-combining biochemical, "crosslinking," and genetic methods-the researchers studied NuA4 and SAGA, two protein complexes of a type known as histone acetyltransferase complexes, or HATs. Gene activation begins when HATs attach to a single gene on a DNA molecule. Although many different proteins comprise SAGA and NuA4, they share just one protein, Tra1.

With a mixture of experimental methods-traditional biochemical and genetic experiments as well as a "crosslinking" experiment, where the use of a purified complex helped distinguish which protein among the many was being recognized by the gene-the researchers showed that the two different complexes were recruited to the gene because they shared that same Tra1 subunit.

According to Workman, the combined approaches and the collaboration with Song Tan, assistant professor of biochemistry at Penn State, created a vibrant research atmosphere as the group worked to understand how the gene-activation process functions under normal conditions in order to provide a baseline of understanding for situations of abnormal cancerous activity.

Identifying Tra1 as the target protein that genes recruit to start the transcription process represents only a part of the researchers' findings, though. As a member of a family of large proteins-"twice the size of a nucleosome, bigger than most proteins by a long shot," Workman says-Tra1's "relatives" include some other proteins that are involved in DNA repair. In addition, the researchers believe only about 25 percent of the Tra1 protein works to fulfill responsibilities as a genetic target, and that leaves a large portion of the protein's duties unknown.

"The protein is so big that it probably does a number of different things," Workman says. "It has a domain that probably recognizes signals somehow from other cells. Also, because proteins related to Tra1 are involved in DNA repair from chemical damage or ultraviolet light, it has other potentially important responsibilities. Our DNA is constantly being repaired and if that does not happen, things such as cancer can happen quickly."

Additional collaborators in the Workman laboratory were: Christine Brown, postdoctoral fellow; LeAnn Howe, postdoctoral fellow; Kyle Sousa, undergraduate student; and Michael Carrozza, postdoctoral fellow. Stephen Alley, a postdoctoral fellow in the laboratory of Stephen Benkovic, Evan Pugh Professor of Chemistry and holder of the Eberly Family Chair in Chemistry at Penn State, provided the crucial crosslinking technology used in the studies.

The research was supported by a grant from the National Institute of General Medical Sciences. In addition, Brown, Alley and Howe receive support from the Leukemia and Lymphoma Society, the National Institutes of Health, and the Canadian Institutes of Health Research, respectively.

Below is a listing of funds within our department. We would of course be very pleased to receive donations toward any of the funds you may choose to support. Following the list of funds are those of you who contributed to any of them in 2001; we greatly appreciate your support.

Paul M. Althouse Memorial Outstanding Teaching Awards
Arthur K. Anderson Memorial Scholarship in Biochemistry
Irving and Jeanne Atlas Scholarship in Biochemistry
Paul and Mildred Berg Graduate Student Travel Endowment
Paul Berg Professorship in Biochemistry
Paul and Mildred Berg Summer Scholar Research Endowment
Malabika Chakravarti Memorial Endowment for Graduate Student Travel in Biochemistry and Molecular Biology
Ming Chu Professorship in Biochemistry and Molecular Biology
R. Adams Dutcher Memorial Scholarship in Biochemistry
Eberly Family Chair in Biochemistry and Molecular Biology
Charles R. Gerth Scholarship in Biochemistry
Kevin Daniel Gilmore Memorial Scholarship in Biochemistry
Ruth Ott Scholarship in Biotechnology
Richard l. Maginnis Memorial Scholarship in Medical Technology
Edward B. Nelson Undergraduate Research Fund in Biochemistry and Molecular Biology
Stanley Person Graduate Fellowship in Biochemistry and Molecular Biology
Stanley Person Professorship in Molecular Biology
Pollard Lecture in Biophysics or Molecular Biology
James W. Shigley Memorial Scholarship in Biochemistry
Stone Lecture in Microbiology
Daniel R. Tershak Memorial Scholarship
Daniel R. Tershak Memorial Graduate Fellowship
Daniel R. Tershak Memorial Teaching Award
Robert Q. and Ida Louise Thompson Scholarship
W. & R. Thompson Scholarship
Frederick C. Wedler Memorial Fund for Outstanding Dissertations
Jacqueline Hemming Whitfield Undergraduate Summer Research Endowment
Verne M. Willaman Professorship/Fellowship

Biochemistry and Molecular Biology Department
Biochemistry Program
Microbiology Program
Medical Technology Program
Summer Symposium in Molecular Biology

Susan M. Abmayr
P. Richard Althouse
Virginia F. Althouse
Anne Gjesdahl Anderson
Arthur K. Anderson, Jr.
Gary M. Aron
Janet M. Aron
Lloyd Arthur
Ruth Ott Arthur
Debra Shigo Barthold
William Barthold
Jonathan B. Basilla
Nancy J. Bigley
Dorothy M. Bomgardner
Lloyd J. Bomgardner
Donald A. Bryant
Dorothy R. Buss
Edward G. Buss
Beverly A. Chapman
J. Donald Chapman
Arthur H. Clagett
Carl O. Clagett
Christopher L. Colbert
Angela R. Coleman
Michael E. Coleman
Matthew K. Cooper
Mary M. Corpe
William A. Corpe
Claude T. Crouser
Arline Elizabeth Culp
Jeffrey S. Culp
Ann M. Daniel
Deborah B. DeLuca
Eric R. Dott
Diana C. Emanuel
Peter A. Emanuel
J. Gregory Ferry
Marilyn A. Ferry
Martin P. Flynn
Dee Frisque
Richard J. Frisque
Elizabeth B. Gilmore

Roger W. Gilmore
Dennis D. Grevel
Molly R. Grevel
Charles E. Grier, III
Vickie C. Grier
Kenneth W. Herko
Fritz Hilton
Mary Hilton
Matthew J. Houser
Jason S. Huhn
David J. Hurley
Enid M. Hurley
Philip B. Inskeep
Susan D. Inskeep
Daryl R. Johnson
Nancy A. Johnson
Linda S. Kao
Teh-hui Kao
Kimberly A. Kelleher
John A. Kirkpatrick
Lois Fekelman Kirkpatrick
Jane E. Klopfenstein
William E. Klopfenstein
Leon J. Kutner
Barbara S. McKee
Richard H. McKee
Leann M. Mohr
Philip W. Mohr
Kimberly A. Moran
Rebecca Morgenson
Erica Mack Moyer
Jeffrey S. Moyer
Edward B. Nelson
Kirsten Ravn Nelson
Barbara Lipo Nichols
B. T. Nixon
Henriette J. Nixon
Philip A. Patston
Sara K. Penfold
Howard T. Petrie
James W. Phillips
Jane Vanwynen Phillips

William D. Phillips
Carol A. Rhoads
Frederic L. Rickett
Pamela M. Rickett
Elaine Robinson Sanders
Marvin T. Sanders
Barbara Anderson Schick
Edwin A. Schick
Peggy L. Schlegel
Robert A. Schlegel
Anita R. Sgrignoli
Barbara P. Shigley
James F. Shigley
Carl E. Sillman
Kathleen A. Sillman
Veronica Stirewalt
Joan Marguerite Tieman
Judith Blackmer Todd
Paul Wilson Todd
Tatsuya Tsukamoto
Richard L. Tyndall
Thelma S. Tyndall
Joan Foster Van Arnam
William Van Arnam
Eric A. Van Venrooy
Susan M. Viselli
Pamela Wagner
Stephen J. Wagner
Dennis L. Welker
Joanne Hughes Welker
Harold B. White, III
Jean Spicer White
Carolyn Whitfield
Charles Whitfield
Jon F. Whitsel
Melissa K. Whitsel
Betty Willaman
Verne M. Willaman
Christopher R. Wronski
Mary Jane Tershak Wronski

Affinity Bioreagents, Inc.
Amgen, Inc.
Clorox Company
GE Fund
GlaxoSmithKline Foundation
Howard Hughes Medical Inst.
Irving and Edythe Grossman Fdn.
Johnson & Johnson
Merck Company Fdn.
Merck & Company Inc.
Novartis Pharmaceuticals Corp
Pfizer Foundation Inc.
Pfizer Inc.
Rohm & Haas Company
Sanofi Pharmaceuticals, Inc.
Schering-Plough Corporation
Schering Plough Research Inst.

C. Leon Harris (Ph.D., Biophysics, '69, Tom Smyth, Jr.) retired from SUNY last June after 32 years teaching biology. He is now writing fiction and teaching materials.

Jack V. Anastasia (Ph.D., Bioch., ’70, Richard McCarl) recently retired as Procter & Gamble Co. Director.

Barbara R. Heard (B.S., Med. Tech., ’73) is a teaching assistant at Western Michigan University. She is currently pursuing a Master’s Degree at Western Michigan University and her area of research is neurobiology.

Allan Khoury (Ph.D., Biophysics, ’72) is Associate Medical Director with Ohio Permanente Medical Group in Cleveland. He is an internist with Kaiser Permanente of Ohio, a 160,000 member HMO, and is in charge of the medical informatics, disease management and health services research programs. He is also the clinical lead for the Kaiser Permanente Population Care Registry, a computerized reminder system in use in Kaiser regions serving 3.8 million members.

Carter B. Schroy (Ph.D., Biophysics, ’78, Paul Todd) is currently a Medical Physicist (Radiation Oncology) with Radiation Management Associates in Bethesda, MD.

Deborah Bonaquist (B.S., Micrb., ’80) is currently a part-time medical technologist with Univera Healthcare and Dr. Ragusa. Her husband, Dante (B.S., Chem. Eng., ’80), works as Director of Research and Development at Praxair in Tonawanda, NY. They have three children.

Christopher C. Carey (B.S., Micrb., ’80) is employed with Accelerated Change Concepts, Inc. in Alpharetta, GA.

Judith Gatesman MacCabe (B.S., Micrb., ’82) decided after graduating to become a fulltime homemaker. She is currently looking after 8 children ranging in age from 22 to 2. Her husband, Thomas S. MacCabe (B.S., CompSci., ’81), is employed as a systems analyst with Dominion VA Power in Richmond.

Alex R. Margin, Jr. (B.S., Micrb., ’80) is currently Project Manager with EG & G Defense Materials, Inc., Chemical Defense Training Facility at Ft. Leonard Wood, MO.

Lauri Ellis Neyer (B.S., MCB, ’89) is Sr. Research Scientist II with Bayer Corp. in Berkeley, CA. She has two children.

Jennifer (Orr) Pluim (B.S., Micrb., ’86) received her M.T. (ASCP) in 1987 from Pennsylvania Hospital and her MBA from Penn State Great Valley in 1995. She lives with her husband, Robert, and two children in Ringoes, NJ. She is currently Scientific Director, Global Marketing & Medical, Anti-Infectives with Aventis Pharmaceuticals, Bridgewater, NJ.

Georgeann Laughman Reilly (B.S., Micrb., ’82) married Ray Reilly in 2000. She received an MBA from Eastern University in 2001 and is currently Director of Risk Management and Safety at the Carlisle Regional Medical Center.

Sandra Rhoads (B.S., Micrb., ’83) received her M.S. in Microbiology from Thomas Jefferson University, Philadelphia, in 1994. She married Joel E. Mortensen, Ph.D. in 1998 and they have a son, Jacob, born in 1999. Sandra is currently employed at Children’s Hospital of Cincinnati.

Sydney Edwards (Ph.D., Bioch., ’94, Ken Johnson) and his wife, Lynn, announce the birth of their first child, Madeleine Sheehan, born in June 2002. Sydney is a Principal in the Biotech practice of TL Ventures in Santa Monica, CA.

Jason G. Krupnick (B.S., MCB, ’91) received his M.D./Ph.D. dual degree in May 1999 from Thomas Jefferson University, Jefferson Medical College in Philadelphia. He completed his Pediatrics Residency at University of California at San Francisco, CA, in June 2002. Last fall he joined Central Bucks Pediatrics in Doylestown, PA. He and his wife, Meredith, welcomed their first child, a son, born in July 2002.

Chad E. Laurence ( B.S., Micrb., ’97) received his Doctorate in Chiropractic from Life University in Manetta, GA, in 2000. He is currently a Chiropractor at Chamberlain Family Chiropractic in West Chester, PA.

Donald de Mackiewicz, Jr. (B.S., Micrb., ’95) recently finished three years in the Peace Corps in Mali, West Africa. He is currently working at Kelly Scientific Services.

Todd Mayover (B.S., Micrb., ’95) completed his Masters in Molecular Biology in 1998 and his Juris Doctor in 2001. He is currently a biotechnology patent attorney in Philadelphia. His practice is focused on the prosecution of life sciences patents.

Amy (B.S., Bioch., ’93) and Amish Mehta (B.S., Bioch., ’93) celebrated the birth of a daughter in October 2001. Amish is an internist in private practice north of Pittsburgh. Amy received her Ph.D. in biological sciences from Carnegie Mellon University in May, 2002, and is taking some time off from science to be a full-time mom for awhile.

Michael D. Perloff (B.S., Micrb., ’96) finished his Ph.D. in Pharmacology in early 2002 and then spent the summer in Berlin, Germany, with his fiancée. He is currently enrolled in the M.D. program at University of Massachusetts.

Stephen M. Rentz (B.S., Bioch., ’90) received his M.S. in Chemistry from Seton Hall in 1995. He is currently Sr. Project Manager with Wyeth Research in Collegeville, PA

Jason T. Snyder (B.S., Bioch., ’97) received his Ph.D. in Biochemistry/Biophysics from the University of North Carolina in May 2002 and got married in July 2002.

Thomas J. Strencosky (B.S., Bioch., ’97) is an Analytical Chemist with Air Products & Chemicals, Inc. in Allentown, PA. He married Heather Butensky last spring. Heather is currently working on her doctorate degree at New York Chiropractic College.

Joanne Macrae Villers (B.S., Bioch., ’93) received her M.A. in secondary education from The University of Mississippi in 1997. She is currently teaching chemistry and dual enrollment biology at Colonial Forge High School in Stafford, VA. Joanne lives in Fredericksburg, VA, with her husband, Steve, and their daughter, Cíara.

Ross Whitwam (Ph.D., MCB, ’97, Tien) is an Assistant Professor of Biology at Mississippi University for Women. He and his partner, Dr. Holly Krogh, are the proud parents of a daughter, Lucy.

Lisa Wray (B.S., BMB/French, ’99) was Research Coordinator at the University of PA Cancer Center in Philadelphia until entering Temple University School of Medicine in Fall 2002.

Julie Jadlowiec (B.S., Micrb., ’00) is currently enrolled in the Biological Science Department Ph.D. program at Carnegie Mellon University.

Matthew Keller (B.S., BMB, ’00) is currently a medical student at Jefferson Medical College in Philadelphia. Last summer he married Karen Neumann (B.S., BMB, ’00). Karen is attending Temple University Law School.

The following undergraduate students graduated as University Schreyer Scholars in 2001/2002:

Emily Dell, B M B, Timothy McNellis, “Overexpression of Cell Death Repressors by Activation Tagging in order to Elucidate the Hypersensitive Response Pathway”

Kelly Elder, B M B, Donald Bryant, “Preliminary Analysis of the Structure and Function of Rubredoxin: Oxygen Oxidoreductase in Synechococcus SP.PCC 7002”

Jennifer Ford, B M B, Andrea Mastro, “Cytokine Production by Rat Intraepithelial Lymphocytes”

Anthony Grippe, BIOTC, Squire Booker, “Production and Characterization of Histidine-Tagged Escherichia Coli Cyclopropane Fatty Acid (CFA) Synthase”

Susan Knight, B M B, Pamela Mitchell, “Gain-of-Function Analysis of Transcription Factor AP-2 in Drosophila Limb Development”

Caroline Shih-Yi Lee, B M B, Sarah Assmann, “Localization of Arabidopsis Thaliana Extra-Large GRP-Binding Protein By Immunoelectron Microscopy and by Green Flourescent Protein as a Reporter Gene”

Emily Moriarty, B M B, Davis Ng, “Isolation of Dislocation-Specific Sec61p Mutant Alleles From the Endoplasmic Reticulum of S. Cerevisiae”

Chet R. Villa, MICRB, Donald Bryant “The Signal Transduction Adaptor Protein Cas and Its Effectors”

Elham Behshad, Ph.D., J. Martin Bollinger , “Central Physiological & Chemical Challenges that Cysteine Desulfurases Face; Kinetic Dissection of a Cysteine Desulfurase from Synechocystis sp. PCC 6803”

Anamaria Craici, M.S., Robert Paulson, “Mutation of the Murine Polycythemia (Pcm) Locus Causes Alterations in Cytokine Signaling Resulting in Myeloproliferative Disease”

Michael Fetchko, Ph.D., Zhi-Chun Lai, “Investigation of a Leucine-Rich Repeat Protein's Role in Cell-Cell Communication”

Ahmed Hassan, Ph.D., Jerry Workman, “Functional Link Between the Yeast SWI/SNF Complex and Histone Acetyl Transferases”

Prabha Iyer, Ph.D., J. Greg Ferry, “Structural and Functional Studies of Acetate Activating Enzymes from Methanosarcina Thermophila”

Bing Li, Ph.D., Joseph Reese, “Transcriptional Regulation of the Ribonucleotide Reductase 3 Gene: TAFIIs and Chromatin”

Yingyun Liu, Ph.D, David Gilmour, “Analysis of Promoter Proximal Transcriptional Pausing in Drosophila”

Matthew Meyer, Ph.D., B. Tracy Nixon, “A Structural Analysis of the Two-Component Receiver Domain of DctD from Sinorhizobium meliloti”

Madhusmita Mitra, Ph.D., Nina Fedoroff, “Large-Scale Gene Expression Data Analysis and Management”

Kristen Neely, Ph.D., Jerry Workman, “Interaction of the Yeast SWI/SNF Complex with Transcriptional Activators as a Mechanism of Promoter Recruitment”

Nicholas Panasik, Jr., Ph.D., Jean Brenchley, “Structural Basis for Themostability and Thermal Dependence of Activity Alpha/Beta Barrel Glycosyl Hydrolases”

Sung-dae Park, Ph.D., B. Tracy Nixon, “A Study of Human Lysosomal Glycosylasparaginase, Gene Organization, Characterization of Four Mutations Involved in Aspartylglycosaminuria, Processing and Functional Analysis of Glycosylation in the Processing”

Xi Wang, Ph.D., Teh-hui Kao, “Characterization of the S-Locus Controlling Self-Incompatibility in Petunia Inflata”

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