Robert F. Kalejta, Professor
Pennsylvania State University, University Park, PA, BS, 1990, Biochemistry
University of Virginia, Charlottesville, VA, Ph.D., 1997, Biochemistry
Princeton University, Princeton NJ, Postdoc, 1996-2003, Molecular Virology and Cell Biology
Positions and Employment
Professor of Oncology and Molecular Virology, McArdle Laboratory for Cancer Research and Institute for Molecular Virology, University of Wisconsin-Madison, 2014-present
Associate Professor 2009-2014; Assistant Professor 2003-2009
Assistant Director, McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 2011-present
Vice-Chair, Institute for Molecular Virology, University of Wisconsin-Madison, 2013-present
Appointments and Affiliations
McArdle Laboratory for Cancer Research – Department of Oncology
The Institute for Molecular Virology
Carbone Cancer Center
Stem Cell and Regenerative Medicine Center
Cell and Molecular Biology Graduate Program
Microbiology Doctoral Training Program
Madison Virology Program
Molecular and Cellular Pharmacology Training Program
Medical Scientist Training Program
Cancer Biology Graduate Program
Awards and Honors
Associate Editor, PLoS Pathogens 2014-2017
Host and Organizer, International Herpesvirus Workshop, Madison, WI, 2016
Assistant Director for Oncology-Institute for Molecular Virology Liaison, 2011-present
Member, Virology – B study section (NIH-CSR), 2011-2015
Vilas Associate, 2011-2012
Ad-hoc NIH VIRB study section, Feb 2011
Ad-hoc NIH VIRA study section, Feb 2010
Editorial Board, The Journal of Virology, 2010-2012
Editorial Board, Herpesviridae, 2010-present
Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Disease, 2006-2011
American Heart Association Scientist Development Grant, 2004-2007
Fellow of the Leukemia and Lymphoma Society, 1997-2000
NIH Cell and Molecular Biology Training Grant T32 GM08136, 1993-1996
CV long form
Growing up there was a field, forest and creek behind my house (which are now gone), and I spent my days catching butterflies, salamanders and toads, likely instilling in me a love of nature. Despite the lack of science education I received in Catholic school (too much praying, not enough thinking), I knew I wanted to be a scientist. I had a partial scholarship offer from the University of Dallas, a Catholic liberal arts college with a campus in Rome (the only real draw), but decided to go to Penn State, like my two brothers (the only financially viable option). I liked both biology and chemistry, so I decided to major in biochemistry. It was still a pretty new curriculum at the time (1986). Other than a senior seminar and independent study (undergrad research) I only had 4 biochemistry courses (2 general, 1 physical, 1 lab). I also took a course called Tumor Virology and Oncology (MCB 480) that I really enjoyed. Years later, my brother found my transcript in the attic of the house we grew up in, and noticed that I got a “C” in the course. He asked me “isn’t that what you do now? I said yes, yes it is.
After my junior year of college at Penn State, I worked a summer internship at Merck. I thought a career in industry would be a fine pursuit until December of my senior year rolled around, and I didn’t have any job offers yet. But I had started doing undergraduate research and discovered the existence of graduate school, so I took the GRE general and subject test (on the same day), and applied to three graduate programs. UC-Santa Barbara turned me down, and UC-Irvine granted me admission but without financial support. Could it have been because of the 11%ile I got on the GRE chemistry subject test (they didn’t yet have a biochemistry or molecular biology test) after taking the general exam earlier in the day? But I did get offered funding at UVA. Off to Virginia!
At UVA I wanted to work with a professor purifying a protein component of the cellular DNA replication machinery, but he had no funding, so instead I went to work with Joyce Hamlin on DNA replication origins. On occasion, people have asked me what it was like to work for a woman. Honestly, I never thought of her as a woman, just as a scientist. Years later I was asked to write a nomination letter on her behalf for an award for women scientists. I almost didn’t, because I think she deserves awards based on her work, not her gender.
Joyce taught me the value of controls (she wouldn’t even look at my data if I didn’t have them) and how to present data. She said you could make good data look bad by presenting it poorly, but you can’t make bad data look good even if you add all the bells and whistles to a presentation. The Hamlin lab was full of great people that taught me a lot. I once asked postdoc Victor Levenson what was in one of the buffers we used, and he started explaining to me the reason every chemical was included. I cut him off saying I didn’t need to know all of that, just what was in the buffer. He replied no, you do need to know the functions of all the reagents in the buffer so that you can troubleshoot if things go wrong. It was a great lesson. One day I asked another postdoc, Hong-Bo Lin, if he could change the buffer in one of my gels that evening. He looked at me and said don’t be lazy. It made me mad but also made me realize that science is hard work and long hours, and no one is going to do it for me.
During graduate school I would go to the library, take the new issues of Cell, Science, and Nature off the shelf, and photocopy the articles I was interested in (yes, it was that long ago). I became enthralled with the cell cycle, and wanted to study the links between the cell cycle machinery and the initiation of DNA replication, with an eye toward inhibiting that process as an anti-cancer therapeutic. I also wanted to learn a new system, so I applied to a diverse set of laboratories. My first choice was Bruce Stillman’s lab at Cold Spring Harbor where I wanted to biochemically study yeast replicators and the newly discovered Origin Recognition Complex (ORC). But his lab was full, so I went to work for Tom Shenk at Princeton. I applied to Tom’s lab thinking I could work on adenovirus E1A, but found out his lab was switching over to a virus I had never heard of, human cytomegalovirus (HCMV). His student, Mansuo Lu, and other labs, had evidence that HCMV modulated cell cycle progression, but no one knew the viral proteins involved or how they worked.
Tom suggested I transfect cells with a series of overlapping HCMV cosmids and monitor their effects on cell cycle progression to identify viral proteins that could modulate cell cycle progression. Joe Baldick in the lab had just discovered that the viral pp71 protein could transactivate viral gene expression, so I included pp71 in the transfections. Joyce had always stressed the importance of controls, so I made sure to transfect pp71 without any cosmid, and found it could stimulate cell cycle progression on its own (an uncommon example of when a control makes, not breaks, an experiment). A motif search using one of the two lab computers shared by the 25 people in the lab identified an Rb-binding LxCxE motif in pp71. Detecting an interaction proved challenging, in part because I always found very low levels of Rb in lysates that co-expressed pp71. When I showed my Western blots to a grad student in the lab, Jill Bechtel, she suggested maybe pp71 was degrading Rb. A search of the virology literature indicated precedence for such a reaction, as HPV E7 induces Rb degradation. I talked with Tom about this and told him that what I really needed to do was a pulse chase analysis for protein half-life, but I didn’t know how to do it. Tom’s reply was so what? Find someone who does know how, get him or her to teach you, and then do the experiment. This incident taught me that there are no excuses for not doing the right experiment.
While I showed that pp71 did indeed induce Rb degradation in a proteasome-dependent manner, I also showed the degradation is ubiquitin-independent. As the 2004 Nobel Prize in chemistry was awarded for the discovery of ubiquitin-mediated protein degradation, I had, and still do have, trouble convincing reviewers that ubiquitin-independent degradation is a true biological phenomenon. A mechanism would help, and we are working on it, but it is difficult to commit the career of a graduate student to an unfunded project that most people believe is an artifact, so progress has been slow.
A paper describing the proteasome-dependent, ubiquitin-independent degradation of the Rb family members by HCMV pp71 and the cell cycle stimulation it caused was, in various revisions, under review in Nature Cell Biology for about 18 months before it was finally rejected. I was heartbroken. At our annual ShenQuist summer retreat, Jim Alwine was our invited speaker, and I talked to him about the data. I don’t remember the exact words, but Jim told me to stop moping around and get the data published. From that I learned that things will not always (maybe never?) go smoothly in your career, but the old cliché is right, what’s important is not how many times you get knocked down, but how many times you get back up. The data was eventually published in three manuscripts, and I moved on to an Assistant Professor position at the University of Wisconsin-Madison with joint appointments in the Institute for Molecular Virology and the McArdle Laboratory for Cancer Research. I’ve always been amazed that a virology institute would give a job to someone who had never done an experiment in a virally infected cell, and a cancer laboratory would give a job to someone who worked on a virus that didn’t cause cancer!
The rest of the story continues to be written (and hopefully published!).