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Laboratory Research

Kabara Cancer Research Institute Hematology/Oncology Research Laboratory

In October 2015, Paraic A. Kenny, PhD, became the second director of the Kabara Cancer Research Institute. Dr. Kenny was previously an associate professor in the Department of Developmental and Molecular Biology at the Albert Einstein College of Medicine in Bronx, New York. He is an internationally recognized expert in the use of sophisticated three-dimensional culture and models to discover and understand the mechanisms leading to breast cancer development, and in devising new approaches for breast cancer therapy. Dr. Kenny's research is focused on understanding the key signaling defects that drive the main subtypes of human breast cancer and understanding the contribution of the microenvironment to breast cancer initiation and progression, as well as the identification and validation of novel therapeutic targets in triple-negative breast cancer, with a strong focus on the role of GRB7 in this disease.

Dr. Kenny's team includes four PhD scientists – Kristopher Lofgren, Megan Girtman, Sreeja Sreekumar and Craig Richmond – and two research technicians. Dr. Girtman's postdoctoral fellowship position is funded by the Norman L. Gillette Jr. Breast Cancer Research Fellowship, established by Don and Norma Vinger in 2005. Proceeds from the Foundation's annual Steppin' Out in Pink walk helped to fully fund the endowment to make this fellowship possible. Steppin' Out in Pink also provides ongoing financial support of our breast cancer research—both in the laboratory and clinical studies. The Kabara Cancer Research Institute, established by the late Dr. Jon Kabara and his wife, Betty, in 2009, funds Dr. Kenny's position. Precision oncology, including interactions with the University of Wisconsin's statewide Precision Medicine Molecular Tumor Board, is a major focus. See a full list of recent publications.

In late 2015, the Kabara Cancer Research Institute added a second research team, led by Dr. Sunny Guin, with a focus on lung and bladder cancer research.

Gundersen Medical Foundation supports basic research in hematology and oncology. In addition to breast cancer research, the laboratory conducts research in a variety of other cancers and blood disorders.


Microbiology Research and Molecular Testing Laboratories

The Microbiology Research Laboratory was established in 1985 to address the growing concern surrounding Lyme disease, a tickborne illness caused by transmission of Borrelia burgdorferi bacteria from infected deer ticks. Early studies focused on determining the risk of contracting the illness in La Crosse and surrounding communities, and subsequent research efforts led to the development of effective tests and vaccines. In addition, several original observations have resulted in multiple commercially-licensed patents.

The laboratory is staffed by full-time scientists and graduate students enrolled in Master of Science in Clinical Microbiology at the University of Wisconsin-La Crosse. In addition to ongoing studies concerning Lyme disease and multiple other tickborne infections, the researchers are studying other infectious microorganisms and currently have ongoing collaborations with several other academic centers. Their efforts to date have yielded >100 publications that include original research findings, review articles, and book chapters.

The Microbiology Research Laboratory also houses a Molecular Diagnostics Testing Laboratory with a diverse menu of molecular diagnostic tests, several of which were developed by the researchers, to assist Gundersen Health System clinicians. The tests provide confirmation of infection by directly detecting an infectious agent using a technique called polymerase chain reaction (PCR). PCR-based tests detect unique nucleic acid sequences within individual genes of microorganisms. The Molecular Diagnostics Laboratory is certified by CLIA to perform the high complexity PCR-based tests and biannual independent inspections ensure the validity and accuracy of the results. The testing menu is expanding regularly in response to emerging infections and recent scientific advances.


Rheumatology Research Laboratory

Basic Science Research

Herpes is familiar because of cold sores and genital lesions caused by herpes simplex virus. But herpes is more than that. Herpesviridae is a large family of viruses, including Epstein-Barr virus, cytomegalovirus and kaposi's sarcoma-associated herpesvirus that cause diseases ranging from a mild rash to cancer.

All humans are infected with multiple herpesviruses by adulthood. Unlike most viruses, herpesviruses are never cleared—that is, the immune system never eliminates these viruses from the body. They persist in certain cells for the life of the host. Most of the time there are no symptoms to reveal the underlying infection. During this period the virus is in a state of latency, however, later in life it can be punctuated by viral reactivation which is frequently associated with severe disease.

For decades, it was assumed that latency was detrimental to the health of the host because it puts the host at risk for reactivation. Interestingly, we've discovered that herpesvirus latency in mice activates the host innate immune system (macrophages and natural killer cells) and thereby provides a potential benefit by increasing the host's resistance against bacteria and tumors.

Our current research aims to understand how, at a molecular level, herpesviruses interact with the host immune system during latency. This work involves the generation and testing of new viral mutants for their ability to alter the host immune system. These studies are pursued in collaboration with Drs. Linda van Dyk and Eric Clambley at the University of Colorado, Laurie Krug at Stony Brook University and Craig Forrest at the University of Arkansas.

We are Recombineering Experts

The ability to clone herpesvirus genomes into a bacterial artificial chromosome (BAC) has improved the efficiency and fidelity of generating targeted mutations in these genomes. Over the past several years, new recombineering technologies have helped to streamline and improve our mutagenesis strategies. These new strategies were pioneered by Dr. Darby Oldenburg, PhD at Gundersen Medical Foundation. She has more than 10 years’ experience creating and characterizing various herpesvirus mutants for use in tissue culture and in vivo studies. Our methods provide robust, rapid and reliable mutations.

We use a combination of methods to create site-specific mutations (e.g. base-change, insertions, deletions, tagging and others) for DNA contained in BACs. We can create new BACs to study novel herpesvirus isolates as well as quickly and efficiently alter viral genomes in exiting BACs. As a result of this work, Dr. Oldenburg maintains a growing collection of herpesvirus BACs and molecular tools to expedite future mutagenesis projects.

The turnaround time (TAT) for a basic mutation such as a small insertion/deletion (less than 1kb) or DNA base substitution is about three weeks. This includes sequence analysis. The mutated virus is transferred to a stable E. coli strain for long-term storage.

We are always interested in new collaborative projects with researchers in the herpesvirus community who would like to have BACs and/or mutants created and characterized using our improved techniques.

To learn more about herpesvirus recombineering, please contact Dr. Darby Oldenburg at dgoldenb@gundersenhealth.org.


Human Studies

In addition to the basic science studies described above, Gundersen Medical Foundation researchers participate in human studies through the CORRONA database and an investigator-initiated study measuring the prognostic value of a novel blood test (called the interferon signature) in patients with autoantibodies in their blood (antinuclear antibodies or ANA).

Some patients with a positive ANA go on to develop systemic lupus erythematosus or another autoimmune disease, yet many remain healthy. Our hope is that this new blood test will help clinicians distinguish between these two possibilities. This study, which enrolled its first subjects from Gundersen Health System in August of 2010, is in collaboration with Dr. Erik Peterson at the University of Minnesota.

Please contact Dr. Douglas White (dwwhite@gundersenhealth.org) for an update and more information

Love + Medicine

Every day, Gundersen Health System staff deliver great medicine plus a little something extra—we call it Love + Medicine.

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