Medicinal researchers and members of the Furge Lab (l-r): Rina Fujiwara, Erran Briggs, Amanda Bolles, and Laura Furge
Laura Furge, the Roger F. and Harriet G. Varney Professor of Chemistry at Kalamazoo College, is the senior and corresponding author of an important scientific paper that includes three Kalamazoo College student co-authors: Amanda Bolles ’14, Rina Fujiwara ’15, and Erran Briggs ’14. The paper is titled “Mechanism-based Inactivation of Human Cytochrome P450 3A4 by Two Piperazine-containing Compounds” and appears in Drug Metabolism and Disposition, a highly regarded, high impact international journal published by the American Society for Pharmacology and Experimental Therapeutics. The research the paper describes, which was conducted in the Furge Lab on K’s campus, contributes the understanding of how some drugs “apply the brakes to” the activity of an enzyme–in this particular case, an enzyme important to the metabolism (or processing) of about half of all medicines! What are the human implications of the work? “Many individuals take multiple medicines each day,” said Furge. “Multiple-drug regimens can lead to unwanted side effects, including drug-induced inhibition of the very enzymes responsible for the metabolism and clearance of other co-administered drugs.” In fact, side effects from drug interactions of polypharmacy therapy are the number one cause of hospitalization in the U.S. “This paper adds in understanding of how certain classes of drugs may cause this type of unfavorable medical event,” said Furge. “New insights will hopefully lead to better prevention in the future.”
The paper includes 13 figures and tables. Furge noted that Bolles, Fujiwara, and Briggs performed all the experiments that lead to those figures, and “all the work was done on the campus at Kalamazoo College. We had all the equipment here needed to complete these studies, and we have already started full swing on another set of experiments for a future publication.” The students have presented parts of the preliminary data at national meetings in the past year, and the research forms of basis of the Senior Individualized Projects for Bolles and Fujiwara.
Such research, and the extraordinary educational opportunities it provides for K students, requires the cooperation, coordination, and collaboration of many funding sources. “This is so important,” Furge stressed. The Richard Cook Fellowship and the Alan and Elaine Hutchcroft Fund (endowments created and supported by alumni gifts) paid for the summer stipends of Fujiwara and Bolles, respectively. The mass spectrometer essential to the experiments was paid for in part by the Hutchcroft Fund and a grant from the Howard Hughes Medical Institute. The research also was funded by grants Furge secured from the National Institutes of Health.
“Drug Metabolism and Disposition is an international journal with a high impact factor,” added Furge. Impact factors measure how frequently manuscripts in a journal are referenced by other authors.
This past spring Professor of Chemistry Jeff Bartz (pictured at left with two students in his laser laboratory) received word that the National Science Foundation would provide a three-year grant to Kalamazoo College so that Bartz’ lab could conduct new experiments to evaluate how the shape of a molecule influences the mechanics of its dissociation into smaller fragments. The work began this summer and involved four students: Mara Birndorf ’16, Jeremy Lantis ’16, Braeden Rodriguez ’16, and Marlon Gonzalez ’17. And there’s nothing quite as effective as complementing classroom work with hands-on real-world experience. “My chemistry classes taught me the fundamentals, but the research is giving me an idea of what a physical chemist does,” said Birndorf. Bartz agrees: one of the great benefits of the NSF grant is its effect on students, who “move from seeing themselves as students to seeing themselves as scientists.” On a typical weekday morning these young chemists are using lasers in the type of experiments that Bartz long ago thought were unlikely to ever be performed here. After all, smaller schools do face the challenges of getting their research swallowed up by larger institutions with more resources (not to mention graduate students) to conduct a project. Despite those challenges, Bartz finds an angle for K to contribute to new scientific work. “We have to evolve if we want to continue to work at the forefront.” Like most new science, what’s going on in Bartz’ lab derives from previous work. Niclas West ’12 presented a talk, “Velocity-mapped ion imaging of methyl nitrite photodissociation,” in 2010 at the 65th International Symposium on Molecular Spectroscopy. Researchers from Texas A&M found the abstract online and approached the K team about the similarities between the two teams’ experimental techniques. The two groups decided to collaborate on the publication of a paper, “A method for the determination of speed-dependent semi-classical vector correlations from sliced image anisotropies,” which included K student co-authors West and Kelly Usakoski ’14. After this paper came out in The Journal of Chemical Physics, Bartz began work on the proposal the NSF funded last spring. “We are looking at information gaps in previous work that our current experimental techniques can help fill,” Bartz said, “sort of testing old experiments in new ways. It’s kind of a K niche we’ve carved out.” (text by Colin Smith ’15)
K student researcher/presenters at the 2014 Experimental Biology Meeting included (l-r): Amanda Bolles, Rina Fujiwara, and Virginia Greenberger. Not pictured is Michael Korn.
Four Kalamazoo College students attended at the 2014 Experimental Biology Meeting: Amanda Bolles ’14, Chemistry; Rina Fujiwara ’15, Chemistry; Virginia Greenberger ’14, Chemistry; and Michael Korn ’14, Biology. Experimental Biology is a joint meeting of six different societies including the American Association for Biochemistry and Molecular Biology (ASBMB) as well as societies for physiology, nutrition, pharmacology, pathology, and anatomy. The meeting provides a great opportunity for students to present their work and attend a variety of engaging scientific talks. More than 15,000 scientists attended the event in San Diego, Calif.
Bolles and Fujiwara presented their research findings during the Undergraduate Poster Competition and during the regular scientific session for ASBMB. Their research involves recent work completed in the laboratory of Professor of Chemistry Laura Furge. That work has shown that two different (but related) compounds inactivate P450 3A4, an enzyme in the liver and intestine that metabolizes (or processes) a major pharmaceutical drug. The titles of the Bolles and Fujiwara posters were, respectively, “5-Fluoro-2-[4-[(2-phenyl-1H-imidazol-5-yl)methyl]-1 piperazinyl]pyrimidine is a mechanism based inactivator of CYP3A4” and “Mechanism-based inactivation of human CYP3A4 by a piperazine-containing compound.” The ASBMB competition includes posters of some 300 students from a variety of college and universities across the country. One grand prize award was presented to a student in each of four research categories (bioenergetics/protein structure, cell biology/developmental biology, DNA/gene regulation, and immunology/microbiology/neurobiology). Bolles won the $500 grand prize in the bioenergetics/protein structure category and was recognized the next day before an audience of hundreds of scientists, educators, and students at the award lecture for outstanding contributions to education. Bolles’s presentation derived from her Senior Individualized Project (SIP), which will be published later this year along with results from co-author Fujiwara.
Greenberger conducted her SIP research in the laboratory of Professor of Chemistry Regina Stevens-Truss. The abstract she presented at the meeting was titled “Bacterial Action of Novel Cationic Peptide Sequences.” As more antibiotic resistance is observed in patients, new sources of antibiotics are being investigated, including short peptide sequences. Greenberger’s work in the Truss lab was aimed at determining the antibiotic activity (and the precise mechanisms of action that yielded the activity) of two newly studied peptide sequences.
Dr. Furge also presented a poster in the ASBMB regular scientific session based on work started last year by Parker de Waal ’13. The work began as part of a course assignment in Furge’s “Advanced Biochemistry” course and grew into an elegant computational study of structural differences between select variants of the drug-metabolizing enzyme P450 2D6. de Waal used molecular dynamics methods to show how subtle differences in the enzyme structure can help explain differences in the metabolizing abilities of the enzymes. The study is being completed by Kyle Sunden ’16. While in San Diego, Furge spent an afternoon at the Skaggs School of Pharmacy at the University of California-San Diego discussing the implications and approach of the study with other scientists in this field.
Korn attended the American Physiological Society (APS) portion of the Experimental Biology meeting. He presented the results of his SIP work (conducted in the laboratory of Dr. Christopher Mendias at the University of Michigan) in the APS Student Poster Competition. Korn’s abstract received the David Bruce Outstanding Undergraduate Abstract Award. The title of his presentation was “Simvastatin reduces myosteatosis following chronic skeletal muscle injury.”
The future is promising for all four of these outstanding student researchers. In the fall, Bolles will enter the University of Michigan Graduate Program in Biomedical Sciences; Greenberger will matriculate to the chemistry department at Pennsylvania State University to begin work on her Ph.D; Korn will attend the University of Michigan Medical School; and Fujiwara will complete her SIP with Furge this summer. She plans to attend graduate school after her June 2015 graduation from K.
Professors Furge and Truss are both members of the ASBMB and attend the annual meeting each year. Truss also directs a National Science Foundation (NSF)-funded workshop for area high school science teachers in connection with the annual ASBMB meeting. This year’s workshop attracted more than a dozen local teachers who learned science and teaching strategies to use in their classrooms. Attendees at the workshop are also eligible for mini-grants to support further development of their teaching after the workshop. A recent article describes the impact of this workshop (which is in its fourth year).
In other meeting news, the Ruth Kirschstein Diversity in Science Award was given jointly to President Freeman Hrabowski III and Professor Michael Summers of University of Maryland-Baltimore County. Professor Summers was the SIP mentor to Erran Briggs ’14 and has worked closely with Professor Truss on the Professional Development and Minority Affairs Committees of ASBMB. Professor Summers also visited K’s campus in 2010 as a Howard Hughes Medical Institute Guest Scholar Lecturer. Given the connections, and important work of Summers and Hrabowski, Professor Truss arranged for Bolles, Fujiwara, and Greenberger to interview Summers for Kalamazoo College’s Arcus Center for Social Justice Leadership’s Praxis Center. Following the interview, Summers treated the students and Truss to lunch overlooking the San Diego Harbor marina! Notes from the interview will be posted on the Praxis website.
Travel to ASBMB for Bolles, Fujiwara, and Greenberger was supported by grants from the Provost Office, the Heyl Foundation (Greenberger), and the ACSJL. Korn’s travel to the meeting was sponsored by grant funds from his SIP advisor and the University of Michigan. Furge and Truss were supported by the Hutchcroft Endowment as well as their NIH and NSF grants, respectively. Next year’s Experimental Biology Meeting will occur in Boston, Mass.
Thanks to a generous gift from The Hearst Foundation, Inc., Kalamazoo College has established the William Randolph Hearst Undergraduate Research Fellowships. These competitive fellowships will provide support for summer research projects for K students majoring in the sciences or mathematics. The goal is to continue the College’s success in preparing individuals for graduate studies and careers in STEM (science, technology, engineering, and mathematics) disciplines.
Eight fellowships will be awarded each year for the next three years beginning this summer 2014. Each award will consist of a $3,000 stipend to defray travel and living expenses. Eligible disciplines include biology, chemistry, physics, computer science, and mathematics. Projects must be investigative and have the goal of generating primary research results. K first-year, sophomore, and junior students are eligible to apply.
Kalamazoo College Upjohn Professor of Life Sciences Jim Langeland ’86, Department of Biology, will serve as faculty coordinator for the program.
The Hearst Foundation and the William Randolph Hearst Foundation are national philanthropic resources for organizations working in the fields of culture, education, health, and social services. The Hearst Foundations identify and fund outstanding nonprofits to ensure that people of all backgrounds in the United States have the opportunity to build healthy, productive, and inspiring lives.
Some recent news about Kalamazoo College professors:
PUBLICATIONS and EXHIBITS
Carol Anderson (Religion) published “The Possibility of a Postcolonial Buddhist Ethic of Wealth,” an article in Buddhist-Christian Studies…Rose Bundy (Japanese Language and Literature) published “Beneath the Moss,” a set of translations by Fujiwara Shunzei, in the new translation journal Transference…Henry Cohen (Romance Languages) published “The Eldorado Episodes of Voltaire’s Candide as an Intertext of Augusto Roa Bastos’ Yo El Supremo: A Utopia/Dystopia Relationship” in Revista De Estudios Hispanicos…Kiran Cunningham ’83 (Anthropology and Sociology) published “Structured Reflection for Transforming Learning: Linking Home and Away,” in the Salzburg Global Seminar’s Creating Sites of Global Citizenship…Péter Érdi (Luce Professor of Complex Systems Studies) co-authored three papers: “The Past, Present, and Future of Cybernetics and Systems Research” in the journal Systems; “An Integrated Theory of Budgetary Politics and Some Empirical Tests: The U.S. National Budget, 1791-2010” in the American Journal of Political Science; and “Anxiolytic Drugs and Altered Hippocampal Theta Rhythms: The Quantitative Systems Pharmacological Approach” in Network: Computation in Neural Systems…Jim Langeland ’86 (Biology) and Blaine Moore (Biology) are co-authors of a paper accepted for publication in Molecular Biology and Evolution that contributes to the understanding of Alzheimer’s disease. The project was partially funded by a GLCA New Directions Initiative and had four Kalamazoo College students or alumni as co-authors (see a recent K News & Events article about this here.)…Amy Lane (Anthropology and Sociology) published “Religion is not a Monolith: Religious Experience at a Midwestern Liberal Arts College,” an article in Journal of College and Character…Sarah Lindley (Art) exhibited her sculptures in shows at Eastern Michigan University, Alma College, and Hope College…Bruce Mills (English) published An Archaeology of Yearning, a book by the Etruscan Press…Siu-Lan Tan (Psychology) co-authored three chapters and served as primary editor for the book, The Psychology of Music in Multimedia (Oxford University Press, 2013).
AWARDS and GRANTS
Kiran Cunningham ’83 (Anthropology and Sociology) has been awarded the 2014 Dr. Winthrop S. and Lois A. Hudson Award, awarded biannually for the purpose of honoring outstanding K faculty members…John Fink (Mathematics) has been awarded the Lucasse Lectureship for Outstanding Teaching at K…Alison Geist (Mary Jane Underwood Stryker Institute for Civic Engagement) was awarded one of the first Kalamazoo County Spirit of Health Equity awards…Binney Girdler (Biology and Environmental Studies) has been awarded grants from the Michigan Botanical Foundation and from the Central Michigan University Institute for Great Lakes Research…Bruce Mills (English) has been awarded a GLCA New Directions Initiative grant for his work on building a civil rights oral history archive…Lanny Potts (Theatre Arts) was awarded the 2013 Wilde Award for “Best Lighting Designer of the Year” in the state of Michigan for his work on “The Light in the Piazza” at Farmer’s Alley Theatre…Regina Stevens-Truss (Chemistry) has received funding from the GLCA Expanding Collaboration Initiative to study digital resources for learning experimental science.
NEW POSITIONS
Alyce Brady (Mathematics and Computer Science) is an Arcus Center Faculty Fellow. She will work collaboratively with universities in Sierra Leone to develop sustainable open-source academic record-keeping software…Reid Gómez is Mellon Visiting Assistant Professor of Ethnic Studies, focusing on campus climate, faculty development, and curriculum development…Starting July 1, 2014, Mike Sosulski (German and Media Studies) will serve as Associate Provost and Paul Sotherland (Biology) will be the inaugural Coordinator of Teaching, Learning, and Educational Effectiveness.
ENDOWED CHAIRS
The following Kalamazoo College faculty members are the recipients of newly endowed chairs: R. Amy Elman, William Weber Professor in Social Science…Laura Lowe Furge, Roger F. and Harriet G. Varney Professor of Chemistry…Gary S. Gregg, Ann V. and Donald R. Parfet Distinguished Professor of Psychology…Ahmed M. Hussen, Edward and Virginia Van Dalson Professor of Economics and Business…Richard Koenig, Genevieve U. Gilmore Professor of Art…Amy MacMillan, L. Lee Stryker Assistant Professor of Business Management…Ed Menta, James B. Stone College Professor of Theatre Arts…Taylor G. Petrey, Lucinda Hinsdale Stone Assistant Professor of Religion.
Regina Stevens-Truss, the Kurt D. Kaufman Associate Professor of Chemistry has written an article updating an idea of hers and the American Society of Biochemistry and Molecular Biology: the HOPES Initiative. HOPES pairs teachers with working scientists so that together they could provide hands-on opportunities to students. “We didn’t anticipate the sweeping impact the program would have across the nation,” wrote Stevens-Truss in the update. The HOPES initiative has resulted in 27 partnerships in 22 cities across the U.S. and has affected the education of more than 3,600 fourth- through 12th-graders.
Three Kalamazoo College seniors presented their Senior Individualized Project (SIP) research at the Midwest Symposium on Undergraduate Research. The event took place at Michigan State University on Saturday, October 5. The students, their presentation titles, and where they did their SIP:
Sara Adelman’s poster (see photo) won the Outstanding Poster Award for Biochemistry. It was titled “Effects of Copper Bipyridine Catalysed Alkaline Hydrogen Peroxide Pretreatment on Lignocellulostic Biomass in the Ethanol Production Process.” Adelman did her research with Professor Eric Hegg ’91 at Michigan State University.
Geneci Marroquin presented a poster titled “Reactions of Cobalt(II) and Nickel(II) Complexes Containing Binucleating Macrocyclic and Pyridine Ligands with Carboxylic Acids: Formation of Binuclear Co(II), Co(II)Co(III), and Ni(II) and Tetranuclear Co(II) and Ni(II) Complexes.” Her research was done in the laboratory of Professor Thomas J. Smith at Kalamazoo College.
Kendrith Rowland conducted his research in the laboratory of Professor Catherine Murphy at the University of Illinois at Urbana-Champaign. Rowland’s poster was titled “High Sensitivity Surface Enhanced Raman Spectroscopy (SERS) Nanoplatform Based on Gold Nanoparticle Aggregates.”
Kalamazoo College Professor of Chemistry Jeffrey Bartz gave an invited talk at the symposium. That talk, “Detecting Cartwheels and Propellers by Velocity-Mapped Ion Imaging,” highlighted the SIP work of Ryan Kieda ’09, Masroor Hossain ’12, and Nic West ’12, as well as the research of Amber Peden ’11, Aidan Klobuchar ’12, Kelly Usakoski ’14, Braeden Rodriguez ’16, and Myles Truss ’17.
Researchers in the Bartz chemistry lab include (l-r): Jeffrey Bartz, Myles Truss, and Braeden Rodriguez.
Myles Truss ’17 and Braeden Rodriguez ’16 are learning a great deal about chemistry during their summer internships in the laboratory of Associate Professor of Chemistry Jeffrey Bartz. Among the lessons is the extraordinary patience and preparation required to run an experiment that shoots lasers at chemical compounds in order to watch how they behave. According to Truss, it’s “a way of seeing” a chemical component “that combines chemistry and physics.” But things don’t always go as planned. Lasers need fixing, problems arise in the “beam machine,” sample preparation may go awry. According to Bartz, when a high tech piece of lab equipment breaks down his response often aligns with the five stages of grief (denial, anger, bargaining, depression, acceptance). And who would have thought chemistry taught that? Rodriguez and Truss are completing data from a Senior Individualized Project begun several years ago, which shows another key element of science–how it builds over time and through collaborations. Part of what they seek through laser “sight” is nitric oxide (NO) released from interesting compounds. Nitric oxide happens to be central to the chemistry research of someone quite close to Truss—his mother, Associate Professor of Chemistry Regina Stevens-Truss, whose research has found nitric oxide to be of great interest in several cascades of chemical events associated with neurodegenerative diseases. Truss and Rodriguez are testing theory, says Bartz, more “pure” science than applied—with two key products nevertheless, Bartz adds: “the research itself, and aspiring scientists like these two young men.” Rodriguez intends to declare chemistry as his major winter quarter of his sophomore year. Truss begins his first year this fall and is leaning toward chemistry as a possible major.
Three student scientists/athletes transitioned from the laboratory to the gridiron on August 16, the first day for Hornet football practice. Jake Lenning ’15 (chemistry major, health studies concentration), Joe Widmer ’14 (chemistry major, biochemistry concentration), and Jake Hillenberg ’14 (chemistry and psychology major, neurosciences concentration) spent the summer doing chemistry research–Lenning in the lab of Professor of Chemistry Greg Slough; Widmer and Hillenberg in the lab of Associate Professor of Chemistry Jennifer Furchak. Lenning’s research involves testing for differences in two variations of a resin known as the Wang Resin. Widmer and Hillenberg were working outside the laboratory on the day I visited. Lenning plays wide receiver for the Hornets, Widmer and Hillenberg are defensive linemen. The 2013 season will be the team’s second on the new Angell Field, and Lenning is excited. “We had a good season last year,” he said, “and that success will be a good foundation to build a great season this year.”
Because its name sounds like a vintage fighter plane, one might think the “Heme Team” that works with this enzyme is a group of pilots or aviation mechanics. But P450 (short for Cytochrome P450) refers to a family of enzymes that do vital work in the human body such as clearance and transformation of pharmaceutical drugs in the liver. And the “Heme Team” (named for heme, an iron-containing chemical component in all members of the P450 family) are four student research assistants working this summer in the chemistry lab of Professor Laura Furge. The team includes Rina Fujiwara ’15 (pictured at left), Amanda Bolles ’14, Mara Livezey ’13, and Parker De Waal ’13.
According to Fujiwara, Cytochrome P450 2D6—one member of the enzyme family—is responsible for the metabolism (think: conversion into a useful form) of some 20 percent of the medicines we take. So it’s definitely a P450 worthy of study—which, of course, means nature made it difficult to grow in a laboratory setting (as sure as the vegetables your mother said were good for you always tasted terrible). In fact, a great many P450 enzymes are intriguing, and the chemical modification of them and their mutations could one day have significant application in making medicines more effective.
Enter the Heme Team. Part of its summer work, says Fujiwara, has been to use recombinant bacteria (bacteria modified to include the DNA of P450 2D6) to grow the enzyme. Then team members try to separate the purified enzyme from the bacterial culture. Last year, they came close to achieving the goal. This year they developed a new protocol in which the bacteria cells (think: P450 factories) grow more slowly. Fujiwara is also doing work to obtain an even more difficult to express mutant version of 2D6, and that work might become the basis of her Senior Individualized Project next year.
On the threshold of her third year at K, the international student from Japan (chemistry major and thinking about a second major in biology) has always loved science, particularly the area of nutrition. This is her first year in the Furge lab, and she loves working with Dr. Furge and her fellow research assistants. “They are great mentors,” says Fujiwara, “and always help me with my many questions, no matter how elementary those questions may seem.” One exciting side effect of her work this summer, she adds, is the enthusiasm it has sparked for cell biology and biochemistry, two courses she is eager to take during her junior year.
Another great side effect is Dr. Furge’s expertise in another kind of chemistry—baking! “She makes delicious carrot cake and blueberry pies and brings them in for her research students,” says Fujiwara. “I love this lab!”
