Drs Ou and Punihaole are Assistant Professors in the Department of Chemistry and are Pipeline Investigators in our Center. Their work focused on the use of novel chemical imaging and rapid electrochemical sensing techniques to assess the pathophysiology of variant amyloid-β fibrils involved in Alzheimer’s Disease and Cerebral Amyloid Angiopathy and is summarized below:

Abnormal function of brain blood vessels and loss of function of brain cells contribute to cognitive decline in older people. These abnormalities are present in two related brain diseases, Alzheimer’s disease and cerebral amyloid angiopathy. In these disorders, fibrils made up of amyloid-b (Ab) peptides are deposited in the brain. These fibrils damage the cells and blood vessels in the brain.  They may cause these diseases and contribute to their severity. This research has two aims. We will develop bioanalytical methods to 1) monitor how Ab fibrils interact with cell membranes in brain tissue and brain blood vessels, and 2) measure molecules released from these interactions that contribute to cell death.  We will develop novel chemical imaging and rapid electrochemical sensing techniques to do this. We hope to understand the effects of Ab fibrils on the progression and outcome of Alzheimer’s disease and cerebral amyloid angiopathy. Our long-term goal is to better understand causes of Alzheimer’s disease and cerebral amyloid angiopathy.  We hope that this will guide the development of medications for prevention and treatment of these conditions.

Mimicking Exercise Intolerance in Human Cardiac Slice Preparations

Dr Matthew Caporizzo is an Assistant Professor in the Department of Molecular Physiology and Biophysics and is a former Research Project Leader in our Center. His work focuses on the molecular mechanisms that stiffen the failing heart and developing a program to test new therapies that reverse pathological stiffening of the heart.

Exertional intolerance is a common early feature of heart disease caused by stiffening of the heart. Developing therapies to soften the failing heart has been hindered by a lack of experimental techniques capable of measuring exertional capacity in isolated cardiac tissue.  The aim of this proposal is to develop the first-of-its-kind working cardiac tissue preparation to assess the role of stiffness on exertional tolerance. Having recently identified microtubule stabilization as a source of stiffness in the failing heart, the Caporizzo lab will leverage this methodology to determine the potential of microtubule-based therapies to improve cardiac performance in an established rat model of heart failure.  To determine the translational potential of microtubule destabilization therapies to the clinic, the Caporizzo Lab will adapt their platform accordingly to assess exertional tolerance in cardiac biopsy samples. This will enable identification of patient pools most-likely to benefit from microtubule destabilization therapies. If successful, our work will provide new pharmaceutical targets and guidance for novel microtubule-based therapy trials currently under development for the treatment of heart disease.

Evaluating Cardiovascular Care Delivery in Cancer Patients and Its Complications

Dr Mansour Gergi is an Assistant Professor in the Department of Medicine, Hematology/Oncology Division and is a Pipeline Investigator in our Center. His work focuses on balancing risks for bleeding and clot formation in cancer patients with cardiovascular disease.

There is a significant clinical knowledge gap on how to balance the risk of bleeding in people with cancer that are at risk for developing blood clots or thrombi. People with cardiovascular disease (CVD) are at greater risk for developing thrombi. The objective of my research is to study how cancer diagnoses affect care for patients under treatment for CVD with antithrombotics. Antithrombotics are drugs that reduce the formation of thrombi in the cardiovascular system. A comparison of antithrombotic therapy outcomes for CVD patients with and without Cancer will be conducted to determine if those with Cancer are at greater risk for bleeding and are treated appropriately to minimize this risk. The goal of this work is to identify cancer-specific risk factors for bleeding in this patient population. These factors will allow clinicians to better assess risks versus benefits when developing a treatment plan for patients with Cancer and CVD.

Pilot Project Leaders: 

Dr. Nicholas Klug is an Assistant Professor, Research Scholar Track, in the Department of Pharmacology and is a Pipeline Investigator in our Center. His current research centers on the role capillary pericytes and endothelial cells play in sensing and signaling within their respective tissues, such as the central nervous system or meninges to determine how ion channels and associated signaling pathways regulate cerebral blood flow, vascular inflammation, and overall tissue homeostasis. 

Dr. Adam Sprouse-Blum is an Assistant Professor of Neurological Sciences, attending physician, a PhD candidate in Clinical & Translational Science and Pipeline Investigator in our Center. His current research centers on understanding migraine pathophysiology through both human and animal studies with the goal of translating these findings into clinical use.

Project Description

Migraine is a neurovascular disorder and the second leading cause of global disability. Unfortunately, the pathophysiology of migraine is incompletely understood, which has hampered our ability to effectively treat it. One of the largest unanswered questions that remains is, where does the head pain of migraine come from? Current theories suggest the head pain of migraine results from changes that occur in the dura mater. The dura is a protective layer that surrounds the brain and spinal cord. It contains a dense network of tiny blood vessels, called capillaries. This dense capillary network provides an enormous surface area in which head pain in migraine may be detected or transmitted, possibly through actions of pericytes – small cells that line capillaries and regulate their diameter and permeability. In this study, we will begin to examine the role dural capillaries may play in migraine pathophysiology utilizing modern imaging and electrophysiology techniques to measure capillary changes before and after application of CGRP or PACAP, molecules that have been implicated in migraine pathophysiology and that are targets for several novel migraine-specific medications.