Richard K. Assoian, Ph.D.

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Professor of Pharmacology
Department: Pharmacology
Graduate Group Affiliations

Contact information
Department of Systems Pharmacology and Translational Therapeutics
421 Curie Blvd.
Rm 805(office)/833 (lab)
Philadelphia, PA 19104-6160
Office: (215) 898-7157
Fax: (215) 573-5656
Lab: (215) 898-7265
Education:
B.A. (Natural Science)
Johns Hopkins University, 1975.
Ph.D. (Biochemistry)
University of Chicago, 1981.
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Description of Research Expertise

Key words

Extracellular matrix, adhesion receptor signaling, mechanotransduction, cytoskeleton, focal adhesions, matrix remodeling, deformable substrata, mouse modeling, tissue mechanics, cardiovascular biology, progeria.


Overview of laboratory research: Mechanobiology of aging and cardiovascular disease

We are cell/molecular biologists and bioengineers interested in understanding how cells sense changes in the physical properties of their microenvironment and how they convert this information into chemical signals, behavior and function. We are particularly trying to understand how changes in substratum curvature and the stiffness of the extracellular matrix (ECM) affect adhesion receptor signaling, the actin cytoskeleton, intracellular forces, and fate decisions such as proliferation and differentiation. We perform mechanistic analyses in cell culture, use genome- and proteome-wide approaches, assess mechanical properties of isolated cells and tissues, and ultimately test physiological and pathological relevance in mouse models of vascular aging and atherosclerosis.

Cell Mechanobiology
The ECM is a dynamic structure that provides chemical, mechanical, and geometric cues to cells. We are using deformable substrata and micropatterning to study the effects of ECM stiffness and curvature on adhesion receptor mechanotransduction, cytoskeletal remodeling, downstream gene expression, proliferation and differentiation.

In vivo Mechanobiology
We place significant effort on mouse models to document the relevance of stiffness-sensing to mammalian biology. We have identified stiffness-sensitive signaling pathways that regulate smooth muscle cell proliferation during the in vivo response to vascular injury, and we have shown that pharmacologic inhibition of arterial stiffening provide cholesterol-independent protection against atherosclerosis. Recent work has focused on MMP12 (a potent elastase) as a inducer of arterial stiffening with age, vascular injury and atherosclerosis. Our newest and growing interest is in the mechanobiology of Hutchinson-Guilford Progeria Syndrome, a genetic disease of premature aging and death associated with arterial stiffening, atherosclerosis and stroke.

In addition to being in the Perelman School of Medicine at the University of Pennsylvania, the Assoian lab is part of the Center for Engineering MechanoBiology (CEMB), an NSF-designated Science and Technology Center. See https://cemb.upenn.edu for details and opportunities for advanced study.

Selected Publications

Liu SL, Bajpai A, Hawthorne EA, Bae Y, Castagnino P, Monslow J, Puré E, Spiller KL, Assoian RK. : Cardiovascular protection in females linked to estrogen-dependent inhibition of arterial stiffening and macrophage MMP12. JCI Insight 4: e122742, 2019.

Yu CK, Xu T, Assoian RK, Rader DJ: Mining the Stiffness-Sensitive Transcriptome in Human Vascular Smooth Muscle Cells Identifies Long Noncoding RNA Stiffness Regulators. Arterioscler Thromb Vasc Biol 38: 164-173, 2018.

Bade ND, Xu T, Kamien RD, Assoian RK*, Stebe KJ* (*co-corresponding): Gaussian Curvature Directs Stress Fiber Orientation and Cell Migration. Biophysical Journal 114: 1467-1476, 2018.

Bade ND, Kamien RD, Assoian RK*, Stebe KJ* (*co-corresponding): Curvature and Rho activation differentially control the alignment of cells and stress fibers. Science Advances 3: e1700150, 2017.

Mui KL, Chen CS, Assoian RK: The mechanical regulation of integrin-cadherin crosstalk organizes cells, signaling and forces. J Cell Science 129: 1093-1100, 2016.

Liu SL, Bae YH, Yu C, Monslow J, Hawthorne EA, Castagnino P, Branchetti E, Ferrari G, Damrauer SM, Puré E, Assoian RK: Matrix metalloproteinase-12 is an essential mediator of acute and chronic arterial stiffening. Scientific Reports 5: 17189, 2015.

Bae YH, Mui KL, Hsu BY, Liu SL, Cretu A, Razinia Z, Xu T, Puré E, Assoian RK. : A FAK-Cas-Rac-Lamellipodin Signaling Module Transduces Extracellular Matrix Stiffness into Mechanosensitive Cell Cycling. Science Signaling 7: ra57, 2014.

Kothapalli, D.*, Liu, S.L.*, Bae, Y.H., Monslow, J., Xu, T., Hawthorne, E.A., Castagnino, P., Byfield, F.J., Rao, S., Rader, D.J., Pure, E., Phillips, M.C., Lund-Katz, S., Janmey, P.A., Assoian, R.K.: Cardiovascular protection by apoE and apoE-HDL linked to suppression of ECM gene expression and arterial stiffening. Cell Reports 2: 1259-1271, 2012.

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Last updated: 02/15/2019
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