Kabara Cancer Research Institute Hematology/Oncology Research Laboratory
In October 2015, Paraic A. Kenny, PhD, became the second director of the Oncology Research Laboratory at 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.
Also joining the Kabara Cancer Research Institute Laboratory in October 2015 was cancer researcher Sunny Guin, PhD. Dr. Guin uses functional genomic and metabolomic screens—research methods that are new to Gundersen—to identify new driver genes of tumor progression and metastasis in bladder, kidney, ovarian and lung cancers. He was previously with the University of Colorado Denver.
Drs. Kenny and Guin were joined in late 2015 by postdoctoral fellow, Kristopher Lofgren, PhD. The 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.
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 Laboratory
The Microbiology Research Laboratory was created in 1985 to address the growing concern surrounding a tick-borne illness called Lyme disease. Early studies focused on identifying the prevalence of the bacterium Borrelia burgdorferi in La Crosse and surrounding communities, and the research effort expanded to include important findings that led to the development of effective commercial tests and vaccines for detecting or preventing the infection. In fact, the Microbiology Research Laboratory’s original observations have resulted in several commercially licensed patents.
The laboratory is staffed by several full-time scientists and graduate students enrolled in the University of Wisconsin-La Crosse Master of Science in Clinical Microbiology program who continue to devote significant effort to studies that concern Lyme disease.
The researchers have expanded the scope of their work to include studies of other infectious microorganisms, and the efforts have led to numerous publications of their research findings and several review articles and book chapters. In addition, the scientists collaborate with multiple academic partners. For example, the laboratory functions as a central-testing facility for a wide variety of cancer studies overseen by the Eastern Cooperative Oncology Group. The researchers are also involved in a statewide study to evaluate the impact of several newly-described sexually transmitted diseases sponsored by the Wisconsin Network for Healthcare Research.
The Microbiology Research Laboratory is a CLIA-certified high complexity testing facility with an expanding menu of molecular diagnostic tests, several of which were developed by the researchers themselves. In fact, their expertise has garnered widespread recognition, which has led to several commercial partnerships to develop more accurate diagnostic tests. Partnerships with Intelligent MDx and EraGen resulted in FDA-approval of commercial state-of-the-art molecular diagnostic tests that accurately detect human cases of swine flu and Herpes simplex viruses, respectively.
Molecular Diagnostic Testing
Confirmation of disease by direct detection of the infectious agent or genetic abnormality has been revolutionized by a technique called polymerase chain reaction (PCR). PCR-based tests confirm the presence of a microorganism or genetic defect by detecting unique nucleic acid sequences within individual genes (organism or self). The Microbiology Research Laboratory is CLIA-certified to perform PCR-based tests and bi-annual independent inspections ensure the validity and accuracy of the results. The listed PCR-based tests are offered routinely, and the menu is expanding regularly in response to emerging infections and recent scientific advances.
Current test menu
- Organism or genetic defect (samples tested)
- Bordetella pertussis (NP swab, bronchial lavage)
- Borrelia burgdorferi (CSF, synovial fluid)
- Anaplasma phagocytophilum (blood)
- Babesia microti (blood)
- Clostridium difficile (stool)
- Herpes simplex I/II (swab, CSF)
- Varicella zoster (swab, CSF)
- Enterovirus (CSF, stool)
- Influenza A/B (NP swab/wash)
- Respiratory syncytial virus (NP swab/wash)
- Cytomegalovirus (urine, plasma)
- Factor II – prothrombin (blood)
- Factor V – leiden (blood)
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.
Specializing in bacterial artificial chromosome (BAC) mutagenesis
The ability to clone herpesvirus genomes into a bacterial artificial chromosome (BAC) has improved the efficiency and fidelity of targeted mutations in these genomes. Over the past several years, new technologies have helped to streamline and improve our mutagenesis strategies. These new strategies were pioneered by Darby Oldenburg, PhD, at Gundersen Medical Foundation. She has more than 5 years’ experience creating and characterizing various herpesvirus mutants for use in tissue culture and in vivo studies.
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 have successfully inserted up to 10kb of heterologous DNA into the MHV68 genome.
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 of the mutated locus/loci and a three-enzyme restriction fragment length polymorphism (RFLP). The mutated virus is then transferred to a stable E. coli strain for long-term storage.
Our method provides robust, rapid and reliable mutations. Our improved techniques have been used by several MHV68 researchers including our collaborators.
The types of mutants that we have successfully created include:
- Specific base pair changes
- Deletion of open reading frames (ORFs)
- Insertion of various TAGs, reporter genes (e.g. green fluorescent proteins, luciferase)
- Deletion and insertion of ORFs into specific sites within the genome
We are always interested in new collaborative projects with researchers in the herpesvirus community who would like to have virus mutants created and characterized using our improved techniques.
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 (firstname.lastname@example.org) for an update and more information