Dr. Pelin Cengiz Awarded 5-Year NIH Grant
Congratulations to Pelin Cengiz, MD, on her recent R01 award of nearly $1.7 million over 5 years from the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NIH/NINDS). Her project, "Sex differences in neurotrophin mediated neonatal neuroprotection: Role of ER alpha," will test the novel hypothesis that sex-specific TrkB phosphorylation is mediated by hypoxia and ischemia (HI) induced ERa upregulation. An improved understanding of the mechanisms underlying sex-based susceptibility to HI will provide new avenues for future development of drug therapies for neonatal HI.
Dr. Emma Mohr Receives NIH/NIAID Career Development Award
Congratulations to Emma Mohr, MD, PhD, on her award from the National Institutes of Health, National Institute of Allergy & Infectious Diseases (NIH/NIAID). This mentored clinical scientist research career development award (K08 AI139341) provides 75% protected time for Dr. Mohr's research with an award of $989,820 over 5 years. Her project, "Defining maternal and neonatal antibody responses in congenital Zika virus infection" aims to define the relationship between the antibody response during congenital ZIKV infection and outcomes of infection. Determining the relationship between the fetomaternal immune response and these different infection phenotypes is critical to defining the immune response which limits fetal harm and can be used to design effective immunotherapies.
Dr. James Conway to Direct New SMPH Office of Global Health
James Conway, MD (Professor, Division of Infectious Diseases and an associate director at the University of Wisconsin Global Health Institute [GHI], is the director of the new Office of Global Health at the University of Wisconsin School of Medicine and Public Health (SMPH).
The new office has a goal of better serving faculty, staff, students and health care providers in the health sciences programs. It will be located in room 1191F in the Health Sciences Learning Center.
Chris Olsen, DVM, PhD, also a GHI associate director, continues to lead the Graduate • Professional • Capstone Certificate in Global Health Program. Programs Coordinator Betsy Teigland, BSN, will continue to manage the certificate program and other international educational opportunities for health science students.
“[The] SMPH has a long history of leadership in global health on this campus and around the world,” Conway says. “This helps clarify and organize our activities with SMPH while maintaining our ties to cross-campus global health efforts.”
The new office is dedicated to working closely with the health professional programs in the SMPH and the schools of Nursing, Pharmacy and Veterinary Medicine. It is the focal point for graduate and professional global health experiences, from the certificate program to interdisciplinary field courses, service-learning opportunities, international clerkships and the Medical Spanish course. Information about these opportunities can be found at education.ghi.wisc.edu.
The office will continue to work closely with GHI to organize and promote global health education, research and outreach opportunities, including the annual Global Health Symposium.
Christine Sorenson, PhD, Awarded Vilas Professorship
Congratulations to Christine Sorenson, PhD, who was recently awarded a Vilas Life Cycle Professorship, supported by the Women in Science & Engineering Leadership Institute (WISELI) and the UW Office of the Provost. This 16-month award, in the amount of $40,000, supports her research entitled, "Bim, Inflammation and Neovascular Age-Related Macular Degeneration." Inflammation plays a causative role in the pathogenesis of neovascular age-related macular degeneration (nAMD), a major vision threatening disease. Unfortunately, the key regulatory events involved and how the recruitment, activation and clearance of macrophages are controlled during the pathogenesis of nAMD is not understood. This funding will allow us to determine how Bim, a cell death initiating Bcl-2 family member, modulates inflammation during nAMD, and whether its loss of expression contributes to standard of care therapeutic failure in patients.
Sondel Lab to Collaborate with Invenra and WARF
The Laboratory of Paul Sondel, MD, PhD, will soon begin a collaboration with Invenra, Inc., a biotechnology company focused on the discovery and development of multispecific antibodies for immuno-oncology, and Wisconsin Alumni Research Foundation (WARF). This collaboration, planned for two years and worth an estimated $400,000 in direct costs to Dr. Sondel's lab, will foster discovery and development of a bispecific antibody therapeutic for the treatment of neuroblastoma. The idea for this collaboration emerged from a previous collaboration between Invenra and Dr. Sondel. See link to full story: https://pipelinereview.com/index.php/2019020170435/More-News/Invenra-and-WARF-Initiate-a-Collaboration-to-Discover-and-Develop-Novel-Therapeutics-to-Fight-Neuroblastoma-in-Children.html
Nicholas Von Bergen, MD, Awarded Grant from Altathera Pharmaceuticals
Congratulations to Nicholas Von Bergen, MD, who was recently awarded $5,000 for his participation in the project, "Intravenous Sotalol in Pediatric and Congenital Patients: A Multi-Center Registry Study." The purpose of this study, sponsored by Altathera Pharmaceuticals and the Pediatric & Congential Electrophysiology Society (PACES), is to evaluate the safety, efficacy, and dosing of IV sotalol in pediatric patients with tachyarrhythmias as well as adults with congenital heart disease.
Pattnaik Lab Uses Stem Cells, Gene Therapy to Correct Errors in Retinal Cells
A research team led by Bikash Pattnaik, PhD (Assistant Professor, Division of Neonatology and Newborn Nursery and Department of Ophthalmology and Visual Sciences; Investigator, McPherson Eye Research Institute) has shown that two novel approaches to treating an inherited eye disease were effective in restoring the function of a vital component of healthy vision.
The study, published in the January 24, 2019, issue of the American Journal of Human Genetics, concerns a disease called Leber Congenital Amaurosis (LCA16), an eye disorder that affects the retina and causes severe visual damage that typically results in childhood blindness. LCA affects two to three children per 100,000. It can result from mutations in more than 20 genes that are expressed in certain retinal cells – specifically, photoreceptors (cells that are photosensitive and react to lightwaves) and retinal pigment epithelium (RPE), a layer of cells that lies just underneath the photoreceptors.
One such gene, known as KCNJ13, is responsible for producing a protein that is a potassium ion channel in the retina. If the KCNJ13 gene is mutated, it cannot produce the protein correctly; consequently, the vital ion channel, which lets potassium ions pass to and out of the cell, does not function properly. And if the channel does not work properly, the photoreceptor cells cannot encode visual stimuli. The result is a gradual progression toward blindness.
The team first created a "disease in the dish” model to test two possible approaches to treating blindness that results from mutations in the KCNJ13 gene. First, they removed skin cells from two people in the same family. One member had been diagnosed with LCA and had two copies of the mutated gene; the other had no symptoms and had only one copy of the mutation. The skin cells were “re-engineered” back to an undifferentiated state and were analyzed. Both types of cells appeared normal in structure.
But, when they matured, the cells from the LCA-affected person lacked the expression of the protein needed for the ion channel to develop and function. The major disease-causing change affecting the retinal pigment epithelium was the lack of this functional channel. The researchers now had a working model of the “disease in a dish.” The cells could not perform one of the key functions of the retinal pigment epithelium.
The team then tried to “rescue” the deficient ion channel through an approach known as “readthrough therapy.” The mutated gene contained instructions that short-circuit the process of translating DNA into a protein. The resulting protein is thus shorter than it should be. The “readthrough therapy” in this case used an antibiotic (modified) to suppress the signal that stops DNA translation.
While only a portion of the cells completely recovered, the finding suggests that the approach shows promise for future treatment.
In addition, the team used gene therapy in the cells to try to re-establish a proper ion channel. They used lentiviruses – a type of virus with a long incubation period – to deliver corrective genetic information to the affected cells. The result was a functioning potassium current and a normal membrane potential – meaning that ions could move in to and out of the cell correctly.
“We have shown in a cell model that both treatments can restore the retinal cells to proper function,” said Dr. Pattnaik. “This is an important proof of concept for these approaches and gives us hope for the value of precision medicine for pediatric blindness.”
The research was supported by the University of Wisconsin Foundation, the National Eye Institute, the UW Vision Core Grant and the Retina Research Foundation M.D. Mathews Professorship.
UW Program for Advanced Cell Therapy Launches First Clinical Trial
For the first time in Wisconsin, a research team will test a personalized cell therapy to treat a common and serious complication in bone-marrow transplant patients.
The UW Program for Advanced Cell Therapy (PACT) will conduct a study to examine a cutting-edge therapy to treat a viral infection faced by up to 50 percent of bone-marrow transplant recipients.
The program’s first study will deploy virus-specific white blood cells to treat lethal cytomegalovirus (CMV) reactivation that can occur after a bone-marrow transplant.
The Food and Drug Administration-approved trial will begin enrolling adult and pediatric patients immediately through a partnership with UW Health, according to Inga Hofmann, MD, an assistant professor (CHS) in the Division of Hematology, Oncology and Bone Marrow Transplant, who is the PACT medical director and principal investigator on the trial.
“While some European countries might offer this type of treatment as standard care, it is considered experimental in the United States. We believe it is critically important to assess these types of cellular therapies through a clinical trial to carefully monitor safety and efficacy,” she said. “It also allows us to continue to learn how we can improve such treatments and how they work.”
Nearly one in three children are already infected with the CMV by age 5, according to the Centers for Disease Control and Prevention.
Five Pediatrics Faculty Members Accepted to SPR
In 2018, five Department of Pediatrics faculty members were accepted as members of the Society for Pediatric Research (SPR).
SPR's mission is to create a network of multidisciplinary researchers to improve child health. Specifically, it works to facilitate active communications among and between researchers; promote research collaborations through mentoring and knowledge sharing; and advocate for funding and policies supportive of research.
Below are the new members:
- Christian Capitini, MD (Assistant Professor, Division of Hematology, Oncology and Bone Marrow Transplant)
- Matthew Harer, MD (Assistant Professor [CHS], Division of Neonatology and Newborn Nursery)
- David McCulley, MD (Assistant Professor, Division of Neonatology and Newborn Nursery)
- Jessica Scott Schwoerer, MD (Assistant Professor [CHS], Division of Genetics and Metabolism)
- Anne Marie Singh, MD (Associate Professor, Division of Allergy, Immunology & Rheumatology)
Drs. Christian Capitini, David McCulley Named Odell Award Winners for 2018 and 2019
Two Department of Pediatrics faculty— Christian Capitini, MD (Assistant Professor, Division of Hematology, Oncology and Bone Marrow Transplant) and David McCulley, MD (Assistant Professor, Division of Neonatology and Newborn Nursery)—have been named winners of the University of Wisconsin Department of Pediatrics Gerard B. Odell Research Award.
Dr. Capitini is the 2018 award winner; Dr. McCulley is the 2019 award winner.
The $5,000 award is given to an assistant or associate professor in the Department of Pediatrics in recognition of outstanding research accomplishments and demonstrated potential for future contributions. It was established in 1994 to honor Dr. Odell's distinguished career in pediatric research, academia, clinical practice and education.
Dr. Capitini was nominated for his outstanding progress as an independent investigator in bone marrow transplant and cancer immunotherapy. In 2018, he received a highly competitive American Cancer Society Research Scholar Grant, his first NIH/NCI R01 research grant, and five additional grants [two each from the St. Baldrick’s Foundation and UW Carbone Cancer Center, and one from the Midwest Athletes against Childhood Cancer (MACC) Fund]. He is also a local leader in cutting-edge clinical research on CAR T cells, and a well-recognized national spokesperson for pediatric cancer cell therapy and immunotherapy.
Dr. McCulley was nominated for establishing an independent research program that studies the genetic and developmental mechanisms of the life-limiting lung and pulmonary vascular defects associated with diaphragmatic hernia. He was the recipient of the James Sutherland Junior Faculty Research Award from the Midwest Society for Pediatric Research (MWSPR), an organization he will lead as president in 2020. He was also recently promoted to a full member of the Perinatal Research Society and was selected to join the national Society for Pediatric Research. Finally, his 2018 article, "PBX transcription factors drive pulmonary vascular adaptation to birth," was highlighted in the February 2018 edition of the Journal for Clinical Investigation and was the recipient of the Perinatal Research Society's Associate Member Research Publication Award.
Drs. Capitini and McCulley will receive their awards at the Odell Lecture this spring.