Astrocyte-Derived Extracellular Vesicles: Epilepsy Promoters, Repressors and Brain Stimulation
Investigators: Lynne Bemis, Ph.D., University of Minnesota Medical School, Duluth Campus; Gregory Worrell, M.D., Ph.D., Mayo Clinic
This team is exploring ways to use vesicles in the brain as “cargo vessels” to transport potential treatments for epilepsy. These vesicles would be aimed at nerve cells in the brain identified as control points during seizures. Research would involve mice and human cells, and the aim is to develop a device that will electrically “tune” the vesicles into becoming therapeutic tools.
Activation of Guanylyl Cyclase-B as a Novel Treatment for Osteoporosis
Investigators: Lincoln Potter, Ph.D., University of Minnesota; Sundeep Khosla, M.D., Mayo Clinic
These researchers are trying to discover why a specialized type of genetically bred mice have strong, thick bones. If they can determine the cause, it may translate into a valuable treatment for osteoporosis. This is an ideal collaboration, as Dr. Potter developed the strain of mice, and Dr. Khosla is an expert on human and rodent osteoporosis.
Targeting Tau Phosphorylation and Missorting to Treat Alzheimer’s Disease
Investigators: Dezhi Liao, Ph.D., University of Minnesota; Michelle Mielke, Ph.D., Mayo Clinic
This group is studying tau proteins in mice and human cells to understand their role in Alzheimer’s disease. The proteins appear in cells prior to the onset of Alzheimer’s and other dementias. The researchers will develop a specific strain of mice to examine two of the domains where tau affects brain synapses and thought processes. The team wants to understand the molecular factors that cause the damage and relate that to human cells already affected. The goal is to prove the concept that blocking tau may be a way to treat Alzheimer’s.
Development of Personalized Microbiome-Based Treatment for Colorectal Cancer
Investigators: Ran Blekhman, Ph.D., University of Minnesota; Khashayarsha Khazaie, Ph.D., D.Sc., Mayo Clinic
This team is exploring how gene mutations in cancer tumors can affect microbes in the gut and how the makeup of those microbes, in turn, alters tumor growth. The researchers are using mouse models to create profiles for the mutations in colorectal cancer and use the knowledge to develop potential microbiome-based treatments tailored to specific tumor genomic profiles.
PET Agents for in Vivo Imaging of Bacterial Infections
Investigators: Valerie Pierre, Ph.D., University of Minnesota; Timothy DeGrado, Ph.D., Mayo Clinic
Do you have an infectious disease, or is it some other kind of inflammation? Right now, it’s difficult to identify infections simply by scanning them in the body. This team wants to develop tracer technology that will change that. The objective is to use positron emission tomography (PET) scans to confirm and diagnose bacterial infections early on, so as to improve treatment and patient recovery. Ultimately, the goal is to develop and commercialize the technology for widespread use.
Testing Susceptibility of ‘Dirty’ Mice to Induction of Asthmatic Disease and Lung Pathology
Investigators: Stephen Jameson, Ph.D., University of Minnesota; Hirohito Kita, M.D., Mayo Clinic
The CDC reports that more than 50 million Americans suffer from allergies and almost 25 million suffer from asthma – the leading chronic disease in American children. Researchers will be testing the “hygiene hypothesis”, which proposes that increased asthma and allergy susceptibility is a consequence of reduced exposure to natural infections, through improved sanitation and antibiotic use. Asthma and allergic diseases can be modeled in mice; however, lab mice are maintained in special facilities in which they are prevented from being exposed to microbes that infect mice in the wild. These researchers will use “dirty” mice to better model the human immune system allowing them to investigate how normal microbial infections affect immune-mediated diseases, including allergic asthma.
Molecular Functional Biomarker in Alzheimer’s Disease
Investigators: Karen Ashe, Ph.D., M.D., University of Minnesota; Ronald Petersen, M.D., Ph.D., Mayo Clinic
The purpose of this project is to determine whether an abnormal form of a brain molecule can be measured to monitor disturbed communication between neurons in the brain in Alzheimer’s disease. Researchers plan to measure a molecule called delta tau-314 in the brain, blood and spinal fluid of patients with Alzheimer’s disease. It is important to study Dtau314, because blocking its formation may repair abnormalities in the brain which are preventing neurons from communicating with each other, causing cognitive problems. Dtau314 may also help diagnose disease and track response to therapies.
Genomic and Small Molecule Screens for Regulators of Liver Steatosis
Investigators: Douglas Mashek, Ph.D., University of Minnesota; Mark McNiven, Ph.D., Mayo Clinic
Obesity is defined as the accumulation of excess fat in the body. A major complication of obesity is that the excess fat accumulates in many different tissues in addition to adipose tissue. Accumulation of fat in the liver, which is common in obesity, although it can occur independent of it, is the defining trait of non-alcoholic fatty liver disease (NAFLD). Structurally, fat is stored in cells in the form of lipid droplets. Understanding how lipid droplets are degraded is a critical step in combating diseases such as NAFLD. This study will use state-of-the-art approaches to discover genes or drugs that regulate lipophagy to control the degradation of lipid droplets. By doing so, they hope to identify potential therapeutic targets for preventing or treating NAFLD and other diseases characterized by excess fat accumulation.
Precision Medicine of Aromatase Inhibitors in Post-Menopausal Women with ER+ Breast Cancer
Investigators: Michael Walters, Ph.D., University of Minnesota; Liewei Wang, M.D., Ph.D., Mayo Clinic
Breast cancer is the most common cancer in women. Approximately 40,000 women die annually from this disease. Estrogen receptor positive (ER+) breast cancer is the most common subtype, and the first line of treatment for this subtype is aromatase inhibitors (AIs). Resistance to AIs is a major reason for disease recurrence and metastatic disease. Researchers from the U of M and Mayo plan to use various techniques to study how and why DNA sequence differences between two individuals would affect response to individual AIs, and how clinicians can use this information to better individualize AI therapy. By better understanding the biology and structure relationship between the drug and its targets, clinicians can design better therapeutic strategies to treat patients who might not respond well to AIs.