Meet Current Grads

Brittany Albaugh

B.S., CELLULAR & MOLECULAR BIOLOGY
GRAND VALLEY STATE UNIVERSITY

Mechanisms of Reversible Acetylation and
Life in Madison, Wisconsin

The laboratory of Dr. John Denu is interested in understanding the mechanisms and biological functions of reversible protein modifications that modulate signal transduction and chromatin function. My main focus is to characterize enzymes involved in the reversible acetylation of non-histone proteins. It has recently been shown that approximately 20 percent of the proteins in the mitochondria are acetylated, many of which have functions in metabolism and oxidative phosphorylation. For example, Acetyl-CoA synthetase 2 is activated by a sirtuin dependent deacetylation reaction, and inactivated by an unknown acetyltransferase. I have been working to identify novel acetyltransferases with non-histone targets, as well as link post-translational modification to regulatory control of the metabolic activities in the mitochondria.

While I was applying for graduate school, the two most important criteria that I kept in mind were: 1) a strong, prestigious biochemistry research program, and 2) faculty, staff, and students that foster an enjoyable learning environment. For me, the Integrated Program in Biochemistry had both of these qualities. The diversity and size of the program provides excellent opportunities for collaboration and the faculty are very approachable for academic advising.

Additionally, I love living in the city of Madison. Madison provides the friendliness of a small town, but also all of the amenities of a large city such as good shopping and great dining. I especially love the fact that Madison is built to accommodate biking, which is an activity my husband and I both share.

Alison Albee

B.S., MOLECULAR BIOLOGY
PURDUE UNIVERSITY

TACCt at UW-Madison

Transforming acidic coiled coil (TACC) proteins are conserved in a wide range of species from yeast to humans. They have been shown to be centrosomal proteins and involved in mitotic spindle assembly. The mitotic spindle is an elaborate macromolecular machine devised by the cell to ensure that the chromosomes are equally segregated during mitosis. Mitotic spindle assembly is an important step in mitosis and errors in the spindle can lead to cell cycle arrest, mis-segregation of chromosomes, and genomic instability, which in turn leads to serious human diseases including developmental defects and cancer. I am interested in the role of the Xenopus TACC homolog, maskin, in spindle assembly.

What first attracted me to the biochemistry department at the University of Wisconsin-Madison was its excellent reputation and exciting science. What kept me here was the city of Madison. The city and university are a perfect complement to each other. The environment has been ideal for personal and professional growth. I have learned to think in a new way and how to better approach problems. I have also had the opportunity to try new activities I never thought I would before, such as skydiving, caving, and mechanical bullriding. Whatever your choice may be, I can't recommend the University of Wisconsin-Madison enough. In addition to the excellent research opportunities the department has to offer, it also has the bonus of being dangerously close to Babcock Hall, famous for their ice cream. On summer afternoons, there is a steady stream of people from the biochemistry building to Babcock for ice cream!

Allyson Anding

B.A., CHEMISTRY-BIOCHEMISTRY
WASHINGTON UNIVERSITY, ST. LOUIS

Mechanism of 4-Hydroxybenzylretinone (4-HBR) Action in Chemotherapy

Vitamin A and its metabolites play essential roles in cellular growth, differentiation, and vision. Retinoids, a class of compounds with structural similarity to Vitamin A, have shown promise as anticancer agents. Although some naturally occurring retinoids, such as all-trans-retinoic
acid (atRA), are proven inhibitors of cancer cell growth, the therapeutic use of these compounds is limited due to undesirable side effects. Because of this, a continuing goal in retinoid
drug development has been to find new
analogs with improved therapeutic indices. N-(4-hydroxyphenyl) retinamide (4-HPR) is a synthetic amide analog of atRA that has shown some success as a chemotherapeutic agent in clinical trials. Though results are promising, the clinical dose of 4-HPR is limited by residual-associated toxicities. This is due, most likely, to the ability of 4-HPR to release atRA via hydrolysis. A new nonhydrolyzable 4-HPR analog, 4-hydroxybenzylretinone (4-HBR), has been shown to be effective in reducing the size and number of mammary tumors in rats and, importantly, has an improved therapeutic profile when compared to 4-HPR. I am interested in uncovering the mechanism whereby 4-HPR and 4-HBR cause cell death in a variety of cancer cell lines as well as determining whether or not other analogs of 4-HPR are able to produce this effect.

When I first applied to the University of Wisconsin-Madison, I was encouraged to do so because of the strength of the program and the wonderful city. Now that I am a student here, I definitely think that both the school and Madison have lived up to the hype! Being a graduate student has given me many opportunities, both inside and outside of the lab. I am surrounded by a number of brilliant scientists and graduate students who are always willing to offer their advice and insight. I have also taken advantage of the many lakes we have through sailing, ice skating and ice fishing – definitely a first for a girl from Louisiana! With all of the outdoor activities Madison has to offer, along with Big 10 sports, there are plenty of things to do to around the city. I couldn’t be happier with the choice I made to come here and I hope that anywhere I end up in the future is able to live up to the high standard that Madison has set!

Katie Bishop

B.S., CELL BIOLOGY-BIOCHEMISTRY
BUCKNELL UNIVERSITY

Madison: Vitamin D and
Triathlon Capital of the Midwest

What first attracted me to the Biochemistry Department at the University of Wisconsin-Madison was its rich history, particularly scientific work with direct application to disease. My research focuses on the transcriptional regulation of Receptor Activator of Nuclear Factor-Kappa B Ligand (RankL), a vitamin D target gene, which is important in skeletal homeostasis and bone remodeling. Increases in RankL expression lead to osteoporosis, or low bone mineral density, while RankL knockout mouse models exhibit compromised immunity and skeletal defects. The vitamin D receptor has been shown to bind at distal enhancer regions upsteam of the RankL transcriptional start site to regulate gene expression. I am currently looking at how activation of the glucocorticoid receptor, the Jak-STAT pathways, and the Wnt pathways regulate RankL transcription and thus influence bone metabolism. My lab is currently using chromatin immunoprecipitation to identify sites of protein binding and reporter assays to determine the effect that these enhancers have on transcriptional regulation. One major research goal is that we can use RankL as a model for general transcriptional regulation and to show that these modular enhancer regions of non-coding genomic DNA are responsible for activation and repression by several pathways.

I originally came to Madison for its amazing research program, but fell in love with the city in the process. Madison is a very unique city in the fact that it can be as big or as small as you want. Students can live downtown in the heart of the city or out in the country, but still be within minutes from campus. I really enjoy the fact that I only have a 10 minute bus ride to campus, but can still look out my back window into a park. One of the biggest draws to Madison was the people and the athletic community. I have experienced a Midwestern hospitality in Madison, where people are very friendly and inviting. I feel like I have developed a solid network of friends within the department and out in the community through sports. There are countless lakes to swim, country roads to bike, and trails to run. Madison hosts one of the 6 Ironman events held in the United States every September. This ultradistance triathlon consists of a 2.4 mile swim, 112 mile bike, and then a 26.2 mile run, all which much be accomplished within 17 hours. Having been involved in the event as a spectator, volunteer, and participant, I can honestly say it is just as inspiring to participate as it is to watch. The entire city of Madison comes alive to support these amazing athletes. Seeing my friends, coworkers, and training partners out on the course is a Madison memory I won’t soon forget.

Daniel Blasiole

B.A., PHILOSOPHY,
FRANKLIN AND MARSHALL COLLEGE
M.A., PHILOSOPHY,
UNIVERSITY OF CALIFORNIA, SAN DIEGO

Cutting-edge science in
a great place to call home

I work on uncovering molecular processes by which the liver regulates plasma lipid homeostasis. The liver plays a major role in controlling plasma lipid levels by both secreting and clearing lipoproteins. It has long been known that the hepatic clearance of LDL and other lipoproteins is largely mediated the LDL receptor. The Attie laboratory discovered a novel role of the LDL receptor in that it also regulates lipoprotein secretion. I use cellular and molecular techniques to investigate how the receptor carries out this function. In addition to studying the LDL receptor directly, I also study the mechanism by which a newly discovered proprotein convertase, PCSK9, promotes the degradation of the LDL receptor. By lowering LDL receptor activity in the liver, mutations in PCSK9 lead to clinical hypercholesterolemia in humans. It is exciting to work in a field in which specific biochemical questions have clinical implications.

I entered graduate school with the aim of studying molecular mechanisms underlying human disease, particularly in the areas of lipid and carbohydrate metabolism. The Department of Biochemistry offers several opportunities for collaboration with renowned researchers within my specific field. In addition, the wide-ranging interests within the department, as well as throughout the UW, provide many opportunities for exploring areas of research with experts outside my specialty.

As a married graduate student with two children (and coming from San Diego), I have found Madison the perfect place to live. It has a balanced mix of big-city amenities with a small-town feel. Any given day in Madison might include cycling in the beautiful Dane County countryside, kayaking in the surrounding lakes and rivers, listening to live music on the shore of Lake Mendota, touring one of the many art museums, or shopping for locally grown vegetables at a farmer’s market. Unlike most cities in the U.S., all of Madison’s amenities are accessible by an extensive network of bike paths, most of which are plowed in the winter!

Graduate school in Biochemistry at UW offers cutting-edge science in great place to call home.

Justin Brumbaugh

B.S., MOLECULAR BIOLOGY
& BIOCHEMISTRY
PENN STATE

Examining pluripotency via
mass spectrometry

Human embryonic stem (ES) cells are unique in that they have the capacity to differentiate into any specialized cell lineage, a characteristic termed pluripotency. For this reason, human embryonic stem cells hold enormous potential, both for fundamental science and for therapeutic purposes. Understanding how stem cells maintain the pluripotent state and are driven to differentiate into different cell types is key for future research and medical applications. To this end, my work brings together biochemistry and a highly enabling analytical technique, mass spectrometry, to study pertinent factors in human ES cells.

Mass spectrometry permits identification, and in some cases quantification, of proteins in a given sample. Coupling high accuracy mass analyzers to emerging fragmentation techniques, namely, Electron Transfer Dissociation (ETD), enables us to determine not only amino acid sequence, but also post-translational modification (PTM). Thus far, we’ve focused mainly on epigenetic changes that occur during differentiation by tracking PTMs on histone H4. Unique to our approach is the ability to identify combinatorial patterns (i.e., we detect distinct arrangements of modifications on the histone tail such that we can study each modification in the context of those around it).

The University of Wisconsin and Madison itself certainly have a lot to offer. UW boasts top-notch programs in all of the biological and physical sciences and IPiB is no exception. The faculty members are leaders in areas like enzymatics, chemical biology, and many more. As a graduate student, I chose to come to Madison because I believe the program offers the best array of fundamental science. From my experience, labs are particularly open to collaboration and work often spans multiple disciplines. I’d be remiss if I didn’t mention the staff and administration, who bend over backwards to help students with everything from relocation tips to payroll information and beyond.

Madison is also an attractive and dynamic place to live. The city is large enough to offer a wide variety of cultural activities, but small enough to get around comfortably and safely. Sandwiched between two lakes, it’s easy to take advantage of numerous clubs set up around water sports. Madison also offers a very active Ultimate Frisbee association (MUFA), running clubs, and numerous other opportunities to stay active and social.

Jackie Fretz

B.S., BIOCHEMISTRY
UNIVERSITY OF NEW HAMPSHIRE

Exploring the Transcriptional Activities of
NFATc1 in Osteoclasts

In bone, homeostasis is maintained through the coordinated actions of the matrix building osteoblast and the mineral resorbing osteoclast. In disease states, these opposing actions become uncoupled. Although the cytokine responsible for stimulating osteoclast differentiation has been identified, we still understand very little about the signaling events necessary for maturation, multinucleation, and activation of these unique cells. My research has been focused on elucidating the mechanisms by which NFATc1 controls gene expression during osteoclast differentiation. To this end, we investigate how NFATc1 participates in the regulation of multiple target genes previously identified as important to osteoclast differentiation, identify novel targets of NFATc1 regulation, and evaluate how the cooperative or inhibitory interactions of other transcription factors and signaling pathways modulate the activity of NFATc1.

I chose the graduate program in Biochemistry at the University of Wisconsin not only for the high rankings of the program and nationally and internationally recognized faculty, but also because of the unique character of Madison. When asking several professors at my undergraduate program what they thought of the University of Wisconsin the unanimous reaction was “Madison! I love Madison!” and after one visit I had to agree. The city uniquely combines the cultural and entertainment scene of a large metropolis while avoiding the congestion and “concrete jungle” trappings of other locations. I love taking in a show at the Overture Center for the Arts, Comedy Club, or Dane County Coliseum, as well as trying new cuisine at the multitude of the restaurants which highlight food from all over the world. At the same time, I go home at night to a quiet neighborhood and a large yard, ride to work on community bike trails, feel safe coming into lab at all hours of the day or night, and escape on the weekends to the nearby state parks.

For the Biochemistry Department itself, I could not have had the chance to work with a more engaging, fun, or personable group of students. There is a real sense of community fostered within members of each incoming class and among students at all levels of their graduate career. Throughout the year, there are a multitude of social events sponsored by the Student Faculty Liaison Committee (SFLC) which reinforce these ties and provide opportunities to catch up with other students who you may not have had the opportunity to connect on a more regular basis. I have met many people with whom I believe I will share life-long friendships, and who I will sincerely miss when my husband and I move on to the next stage of our lives.

Marielle Gruenig

B.S., BIOCHEMISTRY AND MOLECULAR BIOLOGY
UNIVERSITY OF CALIFORNIA, SANTA BARBARA

Regulation of the RecA protein

After growing up in Switzerland, I moved to California for my undergraduate education and to play on the varsity tennis team. Once I began to talk with my undergraduate advisor about graduate school, he urged me to apply to UW-Madison and could not stop praising the school. When I applied to the IPiB program, all I knew about Wisconsin was that it was somewhere in the middle of the US. Despite the drastic change from California climate awaiting me on my interview weekend, I realized that for me Madison was an ideal place to study and to live. Instead of going back to my home country after my B.S., as I had originally planned, I did not want to pass up the opportunity to study at such a prestigious school with such a well-known department.

I started graduate school with a very open mind, not sure which area of Biochemistry in which I would like to specialize. The three rotations in the first semester helped me choose a great lab in which to spend the next years. In the Cox lab, we study the regulation and mechanism of DNA recombination focusing on the RecA proteins from E. coli and D. radiodurans. My project involves exploring different RecA mutants leading to functional defects and studying the RecA regulator protein RecX. We use mainly in vitro assays to look at ATP hydrolysis and DNA strand-exchange properties of RecA.

The faculty are very collegial, which make collaborations not only possible but also enjoyable. The size of the Biochemistry and Biomolecular Chemistry Departments, the support and technology available through the Biotech Center and the many other departments, make research more fruitful with endless possibilities for furthering one’s projects. What influenced me most in my decision to move to Madison was talking to the other graduate students. They convinced me that it is possible to balance the strenuous life of a graduate student with a fulfilling life outside of science.

The city of Madison, with the UW campus at its heart, is the ideal size so that everything is accessible by bike, but still a lot is going on in terms of entertainment and spare time activities. The Terrace is a great place to hang out, and I enjoy running and biking along Lake Mendota and in the UW Arboretum. The Hoofers Club allows people to take up new or familiar activities such as sailing, rock climbing, kayaking, and cross country skiing. I personally have taken up windsurfing, ultimate Frisbee in an intramural league, and whitewater kayaking.

Greg Kabachinski

B.S., BIOCHEMISTRY &
CELLULAR & MOLECULAR BIOLOGY
UNIVERSITY OF TENNESSEE

Score High in the Lab and Low on the Course

Multicellular and higher eukaryotic organisms are composed of cells that have the unique and essential ability to communicate with
each other and respond to a changing environment. Small molecules (i.e., neurotransmitters) and peptides (i.e., hormones) serve as signaling molecules that mediate this communication. Specific spatial and temporal control in signaling pathways are achieved by regulating the synthesis of the signaling molecule, the release of that molecule into the extracellular space, and the response in the target cell.

The process of regulated release, or exocytosis, consists of multiple steps that begin with the packaging of the signaling molecule into a lipid vesicle. This vesicle must be targeted to the plasma membrane by a tethering/docking step and then become fusion competent through an ATP dependent priming step. This is followed by calcium influx that will trigger the fusion of the vesicle with the plasma membrane resulting in the release of the signaling molecule. Despite the identification of many of the proteins involved in this process, the integration of these steps and the exact sequence and events that occur within each step remain unknown. In vitro assays have demonstrated that the 145 kDa protein, known as Calcium Activator Protein for Secretion (CAPS), is required for regulated exocytosis. It has been recently reported that CAPS acts at or around the ATP dependent priming step, but its function and exact role in exocytosis is not yet known. My project is to study the effect of a CAPS deletion in mammalian cells by the use of RNA interference (RNAi). I make use of multiple microscopy techniques, in particular total internal reflection fluorescence microscopy (TIRF), to characterize the phenotype of the deletion and elucidate the functional role of CAPS.

I realized shortly after my recruiting visit that there was no other place I would rather do my graduate work than in Madison. I was very impressed by the collaborative nature of the investigators within the department and across campus. Besides the outstanding research being performed and the impressive resources within the Biochemistry Department, Madison is just a wonderful place to live. This city is so unique. It has the amazing balance of being an extremely active city while still maintaining its small town appeal and charm. Riding my bike to work, sailing with the Hoofers club on Lake Mendota, hanging out with friends at the Memorial Union Terrace, and playing at one of the many golf courses in the area are just a few of the activities I enjoy doing. Before I moved here, I talked to people who had lived in Madison, and every one of them had nothing but positive things to say about this city and school, and I am confident that the same will be true for you.

Mark Marzinke

B.A., BIOLOGY
COLLEGE OF THE HOLY CROSS

Retinoic Acid and the Midwest:
Bringing the Vitamin “A” Game!

The University of Wisconsin-Madison has a long and celebrated history in vitamin biochemistry. My graduate research focuses on one of these vitamins, discovered by Elmer McCollum at UW-Madison, Vitamin A. The metabolites of vitamin A are important in several developmental processes, including vision, cellular differentiation, neurogenesis and reproduction. Vitamin A (as the metabolite all trans-retinoic acid) mediates these processes through the regulation of gene expression. Vitamin A deficiency (VAD) models have shown defects in neuronal development, specifically affecting hindbrain patterning and cranial nerve organization. The goal of my work is to characterize vitamin A-responsive genes that may be important in neuronal development. Building upon research previously conducted in my lab, I am interested in elucidating the biochemical pathways in which these genes potentially participate. I have currently focused on antibody production, knock-down studies in culture, and protein interaction screens to better understand the functional significance of vitamin A-regulated proteins in neuronal development.

I came to Madison, Wisconsin from New York City, and although a self-proclaimed “Coastie”, my experiences at the university and in this city have been tremendously rewarding. Since joining the department, I have become active in the Student Faculty Liaison Committee (SFLC), serving at one point as Social Chair, Recruitment Chair and Vice-Chair. The goal of the committee is to allow the graduate students to have a voice and a role in directing the future of our department, and it has been incredibly successful since its inception. Personally, I have made amazing friendships with labmates as well as people throughout this diverse department and beyond. The more time I spend here, be it going for Gelato on State Street, stopping by Bratfest during the summers, grabbing a locally-brewed beer at the Memorial Union Terrace (or “Il Terrachi” as my friends call it), or attending the Concerts on the Square, the more I think of Madison as home. New York is an amazing place to visit, but my three years in Madison are making me realize that I am not as much of a “big city boy” as I thought.

Phil Raess

B.S., CHEMISTRY
INDIANA UNIVERSITY

A novel role for cholecystokinin in β-cell growth and survival

Our lab studies the molecular genetics
of type 2 diabetes. Although most people with type 2 diabetes are obese, only a minority of obese people develop type 2 diabetes. We can replicate this dichotomy by studying two different strains of mice that are either diabetes-susceptible or diabetes-resistant when made obese. Our lab uses mouse genetics combined with transcriptional and metabolic profiling to identify genes and pathways that confer resistance or susceptibility to type 2 diabetes. My project is focused on the potential role of cholecystokinin as a mediator of diabetes resistance. We identified CCK by performing microarray analysis of pancreatic islets of obese mice.

As a student in the UW Medical Scientist Training Program (MSTP or MD/PhD program), the first two years of study consist of medical school coursework and laboratory rotations. I was attracted to Biochemistry for my lab rotations by the amount of interesting and clinically relevant research taking place within the department. During my rotation in the Attie lab, I knew I had found my thesis lab. After defending my thesis and completing the PhD portion of my education, I will return to medical school to complete my clinical rotations.

I also enjoy spending time outside of lab. Madison has a nice mix of activities – summertime means hanging out at the Union Terrace on the shores of Lake Mendota, watching sailboats and windsurfers as the sun sets. There are frequent outdoor concerts all over town ranging from bluegrass to classical and everything in between. Winter also brings a lot of fun outdoor activities – there are three ski areas within an hour of Madison and lots of opportunities in town to cross-country ski or play ice hockey at local parks. Madison is a wonderful place to train and live, and I will miss it when I move forward with my career.

Brynne Stanton

B.S., BIOCHEMISTRY
UNIVERSITY OF OREGON-EUGENE

It was difficult challenge for me to choose a single graduate program among the several I visited, but when the decision time arrived I enthusiastically settled on Madison primarily because of the interactions I had with faculty members during my interview. Professors made me comfortable enough to talk about ideas and focus on science, rather than trying to intimidate me or make me apprehensive. So even though interviewing can be a stressful experience, the Madison experience was fun and educational. I am currently preparing for my preliminary examination on my research project that focuses on two evolutionary conserved DNA binding proteins'homeodomain proteins'that function in cell type specification in Cryptococcus neoformans, a pathogenic fungus that causes severe health problems in immunocompromised individuals. What I like most about my project is using classical biochemical approaches to study DNA binding proteins that are central to the biology of a medically important organism. The wonderful interactions I have had with students and professors here are why I chose Madison and why my research project has been successful and exciting. I am really grateful for how dedicated the professors are to my scientific development.

Christopher Warren

B.S., BIOCHEMISTRY
NORTHWESTERN UNIVERSITY

Determining the Complete Sequence-Specificity of DNA-Binding Molecules by Cognate Site Identity (CSI) Microarrays

Determining the sequence-recognition properties of DNA-binding proteins and small molecules is a major challenge. To address this need, our lab has developed a high-throughput approach that provides a comprehensive profile of the binding properties of DNA-binding molecules. The approach is based on displaying every permutation of a duplex DNA sequence (up to 11 positional variants) on a microarray. The entire sequence space is interrogated simultaneously, and the affinity of a DNA-binding molecule for every sequence is obtained in a rapid, unbiased, and unsupervised manner. Using this platform, we have determined the full molecular recognition profile of numerous engineered small molecules and eukaryotic transcription factors. The approach has also yielded unique insights into the altered sequence-recognition landscapes as a result of cooperative assembly of DNA-binding molecules in a ternary complex.

The University of Wisconsin-Madison has been a perfect place to develop this technique since this is the home of the inventors of the NimbleGen maskless microarray synthesizer, a technology which has been critical to our early successes. But even more vital to our accomplishments is the interdisciplinary spirit of this university. In our lab alone, we have a biochemist, chemist, engineer, bioinformaticist, geneticist, and molecular biologist all working side-by-side. It is this cooperation that keeps UW-Madison such a high ranking school in so many disciplines. And, of course, I can’t neglect mentioning how much fun Madison can be, whether it’s having drinks out on the terrace or playing weekly kickball or dodgeball games.

Rex Watkins

B.S., CHEMISTRY
UTAH STATE

Protein engineering of ribonuclease A and the investigation of ribonuclease inhibitor function

I arrived in Wisconsin with a chemistry-oriented background and was looking to enter more biological realms. The nucleus of chemical biology talent provided much of the impetus to join the University of Wisconsin Biochemistry Department.

My research is focused on the protein engineering of ribonucleases and better understanding the biological function(s) of its inhibitor protein, ribonuclease inhibitor. The work is rewarding and multidisciplinary – from organic synthesis to molecular biology.

The atmosphere is inviting and collaborative. Faculty members are energetic, talented, and helpful, in part due to a support staff that is second-to-none. The state-of-the-art facilities and infrastructure make the imagination the primary limitation to research. I personally have benefited most from interactions with fellow students.

Madison has been a wonderful choice for me and my family. The university housing is affordable, located convenient to campus, and the neighborhoods are safe. And importantly, there are plenty of opportunities to play basketball.