WELCOME TO THE MCLENDON LAB!
Dr. Jared McLendon is an Assistant Professor of Pharmaceutical Sciences and Experimental Therapeutics at the University of Iowa. Our lab studies cytoskeletal adapter proteins, a class of proteins that help cells sense mechanical forces and translate them into changes in gene expression and cell structure. Using RNA sequencing and transcriptomic analysis alongside functional and structural studies, our long-term goal is to accelerate the development of new therapies that target these proteins for cardiovascular and neurodegenerative disease.
RESEARCH INTERESTS
Cells constantly balance stability and flexibility in their internal scaffolding, the cytoskeleton. Too little remodeling and cells can't adapt to mechanical or biochemical signals; too much and that scaffolding falls apart. This imbalance is a hallmark of conditions ranging from Alzheimer's disease to heart failure to vascular disease. Cytoskeletal adapter proteins help maintain this balance, but we still know very little about how they're regulated in different cell types, which has made them difficult to target therapeutically.
Our primary model is Sorbs2, a single gene capable of producing dozens of distinct protein isoforms. Different cell types build and use different versions of Sorbs2 for very different jobs, and our lab is working to understand how cells make that choice and what each version actually does.
In the heart, loss of Sorbs2 destabilizes the cytoskeleton and weakens contractile function, contributing to progressive heart failure. We study this using live cardiac tissue slices, which preserve native heart architecture and let us directly measure contractile force, calcium handling, and mechanical properties in intact tissue.
In the nervous system, we are asking whether neurons rely on a distinct version of Sorbs2 that also binds RNA, and whether loss of neuronal Sorbs2 contributes to synaptic dysfunction and neurodegeneration, including in models of Alzheimer's disease.
In blood vessels, we are examining how Sorbs2 shapes mechanical signaling in vascular smooth muscle, and how its loss affects vessel contraction and stiffness, contributing to our understanding of vascular disease.
Beyond Sorbs2, we maintain other research threads that share our interest in cell structure and disease. One project explores how centrosomal proteins support the cardiomyocyte's internal scaffolding and protein quality control system, with implications for heart failure. Another investigates how ovarian cancer cells use multiple drug transporter proteins to develop resistance to chemotherapy.
OUR GOALS
Determine how different cell types regulate Sorbs2 isoform expression
Define the functional impact of neuronal Sorbs2
Use live cardiac tissue slices to connect Sorbs2-dependent cytoskeletal remodeling to heart function
Understand how Sorbs2 shapes vascular smooth muscle mechanics and its role in vascular disease
Investigate how centrosomal proteins support cardiomyocyte structure and protein quality control
Identify how ovarian cancer cells use drug transporter networks to develop chemoresistance
COME JOIN US!
We are open to everyone! Whether you are an undergrad, graduate, or post graduate, as long as you are motivated and want to investigate something you are interested in, our lab is a great way to do so. Please contact us at PSET-MclendonLab@uiowa.edu
