Microbiology and Molecular Genetics

Source: 6/17/2009 Medical College of Wisconsin World Newsletter

Researchers at The Medical College of Wisconsin published the first initial paper describing the Milwaukee prevalence of the largest outbreak of novel swine origin influenza virus (S-OIV) in America in the June 11, 2009, online issue of Viruses. This corresponded to the announcement by World Health Organization of the first influenza pandemic in 41 years.

Beginning April 17, 2009, increased numbers of novel swine origin influenza A (H1N1) virus (S-OIV) cases began appearing in the United States. As part of a rapid clinical and public health response, the Medical College and its two affiliated teaching hospitals – Children’s Hospital of Wisconsin (CHW) and Froedtert Hospital – established full genetic subtyping of all influenza A viruses identified in patient samples sent to the respective clinical laboratories. Froedtert Hospital’s testing is performed by Dynacare Laboratories.

The Medical College’s Midwest Respiratory Virus Program (MRVP) used its newly developed multiplex, rapid diagnostic testing for influenza, to subtype all influenza A samples obtained during the 16-week period prior to April 28 and the first four weeks of the subsequent pandemic.

“Continued rapid local surveillance in Milwaukee should help define important epidemiologic and virologic characteristics during the early phase of this pandemic to help facilitate current and future public health responses,” said Kelly J. Henrickson, MD, Professor of Pediatrics and Microbiology and Molecular Genetics.

During the first four weeks of the epidemic, 679 of 3,726 (18.2 percent) adults and children tested for influenza A were identified with S-OIV infection. S-OIV was confirmed on day two of instituting subtype testing and within four days of reports of national cases of S-OIV. Of the 2,678 children and adolescents from whom respiratory specimens were obtained, 598, or 22.3 percent, were positive for influenza A. Of these 598 children and adolescents, 589 or 98.5 percent, identified as S-OIV. During the same four week period, 94 of 1,048 adults, or 8.9 percent, tested positive for influenza A, with 90, or 95.7 percent, having S-OIV.

Dr. Henrickson, who directs the MRVP and practices at Children’s Hospital, and other researchers at other institutions have developed a number of multiplex, rapid, diagnostic tests for respiratory viruses and pneumonia agents including complete influenza subtyping assays. The genetic tests can identify the majority of human and animal influenza strains and can distinguish between sub types such as H1N1, H3N2, H5N1, H7N2, and H9N2.

In response to the federal government's high priority for accelerated research to combat bird flu and bioterrorism, the Medical College and Dr. Henrickson have been awarded five grants and subcontracts totaling more than $12 million from the National Institutes of Health (NIH) and Centers for Disease Control and Prevention (CDC) to develop rapid diagnostic devices to test for avian flu and the majority of potential bioterrorism agents.

The Medical College and Children's Research Institute participated in carrying out the work of these grants.

The test being offered by the MRVP has been approved by the Clinical Laboratory Improvements Act and awaits FDA approval.

Source:  6/1/2009 Chemistry World

In the Chemistry World article entitled "Wider therapeutic possibilities for botulinum toxin" Dr. Joe Barbieri comments on the results of a study he led. 

Read the full article

Source:  5/14/2009 Medical College of Wisconsin World Newsletter

The Medical College of Wisconsin has received a $777,000, five-year training grant from the National Heart, Lung and Blood Institute for a highly interdisciplinary, translational postdoctoral training program focused on inflammation and infection in the development and progression of cardiovascular disease.

Available to PhDs and MDs, this innovative fellowship program is housed in the Medical College’s Biotechnology and Bioengineering Center because of its central focus on the translation of basic science discoveries and technological innovations to disease and clinical medicine. Andrew S. Greene, PhD, Professor of Physiology and Director of the Biotechnology and Bioengineering Center, is principal investigator for the grant. Michael Kron, MD, MS, Professor of Medicine in the Biotechnology and Bioengineering Center, is clinical co-director of the grant.

The training combines an individualized mentoring program via mentoring teams with an individual professional development plan for each trainee. Mentors include outstanding basic scientists from traditional and non-traditional areas, clinical scientists focused on infection and inflammation in cardiovascular disease, and representatives from industry.

“Our training team members are unified in their belief that contemporary fellowship programs must not only give young scientists an outstanding experience at the bench, but must also provide intensive exposure to a variety of technologies and approaches,” Dr. Greene said. “Most importantly, young scientists need mentoring that extends beyond the traditional postdoc-mentor relationship.”

Mentors from the Microbiology and Molecular Genetics department contributing to the success of this program are:

- Joseph T. Barbieri, PhD, Professor of Microbiology and Molecular Genetics
- Jennifer Coburn, PhD, Professor of Medicine (Infectious Diseases)
- Michael B. Dwinell, PhD, Associate Professor of Microbiology and Molecular Genetics
- Dara W. Frank, PhD, Professor of Microbiology and Molecular Genetics
- Scott Terhune, PhD, Assistant Professor of Microbiology and Molecular Genetics in the Biotechnology and Bioengineering Center
- Paula Traktman, PhD, the Walter Schroeder Professor in Microbiology and Chairman of Microbiology and Molecular Genetics

Source: 4/27/2009 Medical College of Wisconsin World Newsletter article

Medical College of Wisconsin Cancer Center researchers have learned that a protein, CXCL12, that normally controls intestinal cell movement, has the potential to halt colorectal cancer spreading. These studies represent a potential mechanism by which CXL12 may slow cancer spreading. Controlling this process could lead to new biological therapies for colorectal cancers.

“Colorectal cancer ranked third in cancer-related deaths in the United States in 2008,” said principal investigator Michael Dwinell, PhD, Professor of Microbiology and Molecular Genetics. “Finding therapies to prevent its spread to secondary organs would increase patient prognosis considerably.”

Luke Drury, a graduate student in the interdisciplinary program for biomedical research at the Medical College, was his research associate. Their abstract was presented at the American Association for Cancer Research meeting in Denver on April 21.

Normal intestinal cells stick to underlying proteins, which provide survival signals to maintain cell health. If they become unstuck, the floating cells undergo a programmed cell death.

In cancer, cells have acquired genetic changes that allow them to survive during loss of attachment. Previously, the researchers found that colorectal cancer cells lacked CXCL12 expression. In these studies, they re-introduced CXCL12 expression in colorectal cancer cells which prevented their ability to adhere to underlying proteins. Plus, the floating cells underwent programmed cell death.

This research was done in the Medical College’s Bobbie Nick Voss Laboratory of Colon Cancer Research with funding provided by the National Institutes of Health (NIH), the MCW Cancer Center, and the Bobbie Nick Voss Foundation.

Source: 3/11/2009 Milwaukee Journal Sentinel

Two faculty from the Microbiology and Molecular Genetics department were featured in an article by the Milwaukee Journal Sentinel.  Both Dr. Dara Frank and Dr. Li Wu discuss applications for NIH funding made possible by the American Recovery and Reinvestment Act.  Dr. Frank's proposal is for a cell sorting machine, and Dr. Wu is seeking grants to further his lab's HIV research.

Read the full article

Source:  3/6/2009 Medical College of Wisconsin World Newsletter article

March 6, 2009 College News - The Medical College of Wisconsin is the 9th best university or medical school for postdoctoral fellows to work in the United States, according to The Scientist’s 2009 “Best Places to Work for Postdocs” survey.

The top ten academic institutions ranked in the survey are:
1. University of Minnesota, Minneapolis
2. Vanderbilt University, Nashville
3. University of Iowa, Iowa City
4. University of Texas M.D. Anderson Cancer Center
5. Mayo Clinic, Rochester, MN
6. Oregon Health & Science University, Portland
7. University of Michigan, Ann Arbor
8. Emory University, Atlanta
9. Medical College of Wisconsin
10. University of Texas Southwestern Medical Center, Dallas

The magazine received 3,438 responses from postdoctoral researchers at institutions around the world.

Respondents rated a valuable training experience, access to research equipment and library services, and a good mentoring relationship as the ingredients that make for a good workplace.

The Medical College of Wisconsin has approximately 200 postdoctoral fellows conducting research in the life sciences. The Office of Postdoctoral Education was created several years ago to be an advocate and resource for the College’s postdoctoral fellows. The activities of the office are carried out by Philip S. Clifford, PhD, Associate Dean of Postdoctoral Education, and Catie Bauer, Administrative Assistant, in consultation with the Postdoctoral Advisory Committee.

Full survey results appear in the March 2009 issue of The Scientist.
 

Source: GMToday.com

High school senior participates in two-year research program guided by Dr. Joseph Barbieri after being inspired to medical field by her mother’s battle with cancer.

Entire Article

Source: 12/24/2007 Medical College of Wisconsin World Newsletter article

The Medical College of Wisconsin has received a two-year, $165,970 grant from the National Institute of Neurological Disorders and Stroke to study botulism, a disease that can weaken or paralyze skeletal muscle. The disease is caused by intoxication with botulinum neurotoxin (BoNT), one of the most poisonous substances in the world.

Michael R. Baldwin, PhD, a postdoctoral fellow in Microbiology and Molecular Genetics, is principal investigator for the grant.

Dr. Baldwin will identify and characterize the BoNT nerve cell receptor proteins to understand how BoNTs bind and enter into nerve cells. Using molecular modeling and bioinformatics to identify the receptors will provide opportunities for the development of therapies to fight against BoNT intoxication as well as improved clinical therapeutic methods that use BoNTs.

Source: 12/24/2007 Medical College of Wisconsin World Newsletter article

Scott Terhune, PhD, has been appointed Assistant Professor of Microbiology and Molecular Genetics at the Medical College of Wisconsin. His research interests include identifying how viral proteins from the cytomegalovirus manipulate human cells during infection. 

Cytomegalovirus infects and lies dormant in most people, but can emerge as a serious illness in people with weakened immune systems, such as transplant patients, AIDS patients and some newborns. The only treatment doctors currently have for the virus is an antiviral drug called gancyclovir.

Further understanding of the virus is important because approximately half of all organ or bone marrow transplant patients experience some complication with cytomegalovirus. Women who experience a reactivation of cytomegalovirus or become infected with it during pregnancy risk passing it on to the fetus. This can lead to birth defects, including deafness and mental retardation.

Dr. Terhune comes to the Medical College from Princeton University in New Jersey, where he recently completed a postdoctoral fellowship. While at Princeton, he was also an instructor of molecular biology.

He has authored or co-authored eight journal articles. He received his PhD in biological sciences from the Northwestern University Medical School in Chicago in 2000.  He received his bachelor of arts from Northwestern University in Evanston, Ill., in 1991.

Source: 10/1/2007 Medical College of Wisconsin World Newsletter article

The Medical College of Wisconsin has received a five-year, $1.8 million grant from the National Institutes of Health (NIH) to study the injection of toxins into epithelial cells by a bacterial pathogen. These studies may ultimately provide opportunities to develop therapeutics that prevent damage to tissues and limit bacterial growth. The grant is from the NIH's National Institute of Allergy and Infectious Diseases.

Dara W. Frank, PhD, Professor of Microbiology and Molecular Genetics, is principal investigator for the grant. Dr. Frank is also director of the Medical College's Center for Biopreparedness and Infectious Diseases.

She believes that the localization of a cofactor for membrane integrity may govern the toxin's biologic activities and promote either colonization or spreading at certain stages of bacterial invasion. Understanding how eukaryotic elements critical to bacterial toxin activity work together will allow the development of inhibitors that interrupt the natural progression to serious infections. This may result in a combination of therapies that could help patients who are critically ill or in the early stages of chronic infection.
 

Source: 1/22/2007 Medical College of Wisconsin World Newsletter article

 In response to the federal government's high priority for accelerated research to combat bird flu and bioterrorism, the Medical College of Wisconsin has been awarded a five-year, $8.1 million grant from the National Institutes of Health's Institute of Allergy and Infectious Diseases (NIAID) to develop a rapid, miniaturized, automated diagnostic device to test for avian flu and the majority of potential bioterrorism agents. The device would be used in an outpatient setting.

The new integrated device the researchers are developing may allow cost effective, point-of-care diagnosis of these agents within one to two hours, according to principal investigator Kelly Henrickson, MD, Professor of Pediatrics and Microbiology and Molecular Genetics at the College. Dr. Henrickson is also a pediatric infectious disease specialist at Children's Hospital of Wisconsin.

Dr. Henrickson previously developed the Hexaplex diagnostic test, using specialized reagents and genetic data for rapid, accurate simultaneous detection of the seven most common lower respiratory viruses, including several varieties of influenza.  This technology is the basis for an array of products for physicians worldwide to rapidly detect the microbes responsible for a variety of illnesses such as aseptic meningitis, chicken pox, chronic cough syndrome, encephalitis, herpes, influenza, pneumonia, SARS, shingles, and West Nile virus.

"Our laboratory has pioneered a flexible, rapid, sensitive and specific method of simultaneously detecting multiple pathogens," said Dr. Henrickson. "We have recently developed two BioTplex assays that detect many (15) category 'A' bioterrorism agents. However, new amplified DNA detection and nucleic acid purification methods beyond those used in the Hexaplex diagnostic test allow for the development of a single 'point-of-care' device that may enhance the speed, flexibility, throughput, and cost effectiveness of multiplex assays."

Infectious agents identified to pose the greatest potential threat (Category "A" agents) include Variola major (smallpox), Bacillus anthracis (anthrax), Yersinia pestis (plague), Clostridium botulinum toxin (botulism), Francisella tularensis (tularaemia), and a group of RNA viruses that cause hemorrhagic fevers (VHFs).

Another agent of grave concern is avian flu. Additional concern exists over bird-to-human spread of avian flu and the potential adaptation for human-to-human spread. Terrorists could take advantage of avian flu's flexibility and engineer more virulent strains capable of causing worldwide pandemics. Current diagnostic assays are directed to the common human isolates of influenza A, but no assay is available to detect all of the avian varieties of influenza A, according to Dr. Henrickson. 

The Medical College of Wisconsin, Children's Hospital, Children's Research Institute and Nanogen Inc. will participate in carrying out the work of the grant.
 

Source: 6/26/2006 Medical College of Wisconsin World Newsletter article

Paula Traktman, PhD, Walter Schroeder Professor of Microbiology and Chairman of Microbiology and Molecular Genetics, received a one-year, $496,375 grant from the Natural Center for Research Resources to purchase a new electron microscope. The grant application featured the work of five major and nine minor users; the microscope will be situated in the shared Electron Microscopy Facility and will enable College faculty to perform state-of-the art ultrastructural studies.

The new microscope, a JEOL 2100 LaB6 Transmission electron microscope, is equipped with a GATAN Ultrascan 1000 digital camera. The microscope has capabilities the College's existing microscope does not have, including digital image acquisition, multi-specimen holder, motorized 5-axis precision goniometer, 200 kV emission current and remote access microscopy.
The software package provided with the camera has the capability of generating tomographic reconstructions and enables image acquisition and analysis.

Abstract for JEOL 2100 LaB6 Transmission Electron Microscope and GATAN Ultrascan 1000 Camera.
 

Source: 3/20/2006 Medical College of Wisconsin World Newsletter article

The Medical College of Wisconsin has received a five-year, $378,750 grant from the National Institute of Allergy and Infectious Diseases to find the factors that make the bacterium Francisella tularensis highly infectious. Infection with this bacterium can cause tularemia, a plague-like disease primarily found in rodents that can be transferred to humans.

Dara Frank, PhD, Professor of Microbiology and Molecular Genetics, is principal investigator of the grant, titled Regulation of Gene Expression in Francisella. Dr. Frank is also director of the Medical College's Center for Biopreparedness and Infectious Disease. Thomas C. Zahrt, PhD, Assistant Professor of Microbiology and Molecular Genetics, is a co-investigator.

There is currently no licensed vaccine to protect against F. tularensis infections, to which humans are highly susceptible. The bacterium can enter a host through broken skin, the eyes, throat or lungs. Additionally, the bacterium was turned into a weapon in the past, making the development of vaccines and the identification of therapeutic agents particularly urgent.

The goal of this research is to genetically engineer strains of this bacterium suitable for the design of a new vaccine.
 

Source: 7/11/2005 Medical College of Wisconsin World Newsletter article

Joseph T. Barbieri, PhD, Professor of Microbiology and Molecular Genetics, has been appointed Director of the College's Medical Scientist Training Program (MSTP) by Michael J. Dunn, MD, Dean and Executive Vice President.  Dr. Barbieri succeeds Dr. David Warltier, who stepped down after being appointed Chairman of Anesthesiology.

Dr. Barbieri has served as Associate Director of the program since 2000.

"The Medical Scientist Training Program is a valuable asset of the College because it helps us to invest in the physician-scientists of the future," said Dr. Dunn.  "Through his successful effort as Associate Director, Dr. Barbieri has proven his understanding of and dedication to training people with this dual degree. He will be effective in expanding upon the success Dr. Warltier had during his tenure."

The MSTP is a comprehensive, seven-year program established in 1983 for students who desire to become physicians and biomedical researchers.  It combines the curricula of the medical school and graduate school and enables trainees to earn both an MD and a PhD.  MSTP graduates continue residency/fellowship training, and many have obtained faculty positions at a variety of medical centers.

"We are fortunate to have leaders at the Medical College of Wisconsin who are truly committed to the success of this program," said Dr. Barbieri.  "It is an honor to have the opportunity to guide the Medical Scientist Training Program."

Dr. Barbieri's research focus is on microbial pathogenesis.

He received his PhD in Microbiology from the University of Massachusetts at Amherst, and completed a Postdoctoral fellowship in the University of California- Los Angeles in the Microbiology Department.  He joined the Medical College faculty in 1986 as an Assistant Professor.    

Source: 11/1/2004 Medical College of Wisconsin World Newsletter

Note: Dr. Joseph T. Barbieri, a member of the Department of Microbiology and Molecular Genetics, received one of the 21 grants for work on high-throughput crystallization robotics.

The Medical College of Wisconsin has awarded 21 grants through Advancing a Healthier Wisconsin to support education and research initiatives at the College. The five education projects and 16 research projects total $4.8 million.

Advancing a Healthier Wisconsin is the College's five-year plan to develop statewide public and community health collaborative projects and research and education initiatives. The projects and initiatives utilize a portion of the $304 million the College derived from the conversion of Blue Cross and Blue Shield United of Wisconsin to a stock insurance company.

Over the next three to five years, $30 million of the $304 million will be available for immediate expenditure in accordance with the plan. The remaining funds will be part of the Medical College's permanent endowment to assure their use in perpetuity.

The plan allocates 35 percent of the funds to the Healthier Wisconsin Partnership Program, which is dedicated to community-medical school collaborations. The other 65 percent of the funds are allocated to health improvement through education and research, which these 21 grants fall under.

To view a list of the projects that were funded, the principal investigators of those projects and the amount and length of funding for each project, click here.

Recipients of the first grants provided through the Healthier Wisconsin Partnership Program will be announced in January. 

Source: 6/14/2004 Medical College of Wisconsin World Newsletter

KaloBios, a therapeutic antibody company, has exclusively in-licensed a preclinical antibody drug and its intellectual property portfolio for the clinically relevant pathogen Pseudomonas aeruginosa. A team of researchers at the Medical College of Wisconsin and the University of California, San Francisco, developed the antibody, which cripples the microbes that have become increasingly resistant to antibiotics.

Multi-drug resistant Pseudomonas is one of the most serious and difficult hospital-acquired infections to treat and affects patients with ventilator-associated pneumonia, cystic fibrosis, low white cell counts, burns and diabetic ulcers.

There are approximately 665,000 patients placed on ventilators in the United States each year, and approximately 200,000 develop pneumonia. The additional patient costs associated with pneumonia in the intensive care unit is $40,000 per patient.

"We are delighted that our findings can move to the next step that could lead to a drug aimed at helping thousands of patients," said Dara Frank, PhD, Professor of Microbiology and Molecular Genetics at the Medical College of Wisconsin, Director of the Center for Biopreparedness and Infectious Disease and lead researcher.

The monoclonal antibody has a unique target mechanism. It neutralizes the action of the PcrV protein of the type III secretion system, inhibiting a key disease-causing process of Pseudomonas. Because the target mechanism is different from that of other antibiotics, cross-resistance is not observed.

Independent research from two groups published in the Journal of Infectious Disease in 2001 and Critical Care Medicine in 2002 directly link the expression of the type III secretion system to poor clinical outcome in Pseudomonas lung infections.

KaloBios is using its proprietary antibody technology to engineer a high affinity human antibody against the PcrV protein that is more potent than the original mouse antibody. The company expects to complete the antibody engineering work by mid-2004 and enter a lead compound into IND Track development at that time.

"We are happy that the Medical College and UCSF have both entrusted KaloBios with the development of this potentially valuable drug. It fits perfectly into the profile of KaloBios' pipeline, where our technology can rapidly generate human antibodies from rodent antibodies that have excellent preclinical validation," said Dr. Geoffrey Yarranton, CEO of KaloBios. The antibody will be used as both a prophylactic and as a treatment for Pseudomonas infections in ventilator-associated pneumonia and cystic fibrosis patients.

"We are excited with KaloBios' capability to engineer and move this drug to the clinic as quickly as possible. People need new approaches to treat infections by this formidable and versatile pathogen", said Jeanine Wiener-Kronish MD, professor of anesthesiology at UCSF.