Steven S. An, Ph.D.

Steven S. An, Ph.D.

Director of Bioengineering, Rutgers Institute for Translational Medicine and Science, Professor of Pharmacology, Robert Wood Johnson Medical School, and Member of Rutgers Cancer Institute of New Jersey, and the New Jersey Alliance for Clinical and Translational Science (NJ ACTS) Academy of Mentors

 

Rutgers Institute for Translational Medicine and Science
Child Health Institute of New Jersey
Rutgers, The State University of New Jersey
89 French Street, Suite 4275
New Brunswick, NJ 08901

(732) 235-9132
sa1510@rbhs.rutgers.edu

Education: Ph.D., Brown University, Providence, RI
B.A. University of Virginia, Charlottesville, VA

Postdoctoral Fellowship: Harvard University, Boston, MA

Dr. Steven S. An, Ph.D. is Professor of Pharmacology and Director of Bioengineering at the RITMS.  Dr. An is an Elected Fellow of the American Thoracic Society (ATS) and has served the Society and its over 77,000 membership as Member of the International Conference Committee and Chair of the Respiratory Structure and Function (RSF) Program Committee. His service to RSF Assembly also includes serving as member of its Planning Committee and its Nominating Committee. He has specific expertise in G protein-coupled receptor (GPCR) signaling and excitation-contraction coupling mechanisms of airway smooth muscle shortening in the context of obstructive lung diseases.

Research Focus:

We aim to understand the mechanobiology across the length scale–how cells and tissues grow, contract, move, invade, and remodel. Understanding the underlying mechanisms of these fundamental biological processes can provide new approaches to tissue regeneration and therapy for diseases such as asthma and cancer.

We develop new technologies to modulate and visualize the physical forces in living cells. The laboratory of Dr. Steven An has the unique capability to map the cellular stress using Fourier transform traction microscopy (FTTM), to probe the material properties of living cytoskeleton using optical magnetic twisting cytometry (OMTC), and to quantitate the molecular-level remodeling of internal structures using spontaneous nanoscale tracer motions (SNTM). These live-cell micromechanical methods are readily applicable to a wide variety of cell types and have broad research applications that are at the interface between engineering, cell biology and medicine.

Recently, we have developed a new micro-physiological system that reconstitutes 3D co-cultures of human airway smooth muscle cells with clinically-relevant human airway epithelial cells that are fully differentiated in an air-liquid interface (Nat. Biomed. Eng. 2019). This “bronchi-chip” is fully equipped with OMTC enabling the interrogation, in real-time, of the interplay between chemical and mechanical cues, and the heterotypic cell responses, driving asthma-like phenotype.

We explore new paradigms in sensory physiology. We have discovered ‘sensory’ GPCRs of the bitter taste receptor (TAS2R) family and the olfactory receptor (OR) family expressed on the smooth muscle of human bronchi (Nat. Med. 2010; Sci. Rep. 2016; Cell. Signal 2018). TAS2Rs effectively reverse bronchoconstriction by a localized calcium flux that activates, in large part, Ca2+-activated K+ (BKCa) channels–evoking membrane hyperpolarization and smooth muscle relaxation. Human airway smooth muscle cells also express multiple ORs and their obligate downstream olfaction machinery. Of note, activation of OR51E2 via its cognate ligands acetate and propionate results in marked reductions in cytoskeletal remodeling and cellular proliferation. These physiologic outcomes mediated by endogenous metabolic byproducts of the gut microbiota suggest previously unidentified “ancient” chemosensors of the gut-lung axis. The findings also give rise to the notion that ectopic expressions of sensory receptors can be exploited to discover novel disease-modifying therapeutics for asthma.

Current research efforts include: 1) identifying molecular machines primed for sensation in the lung; 2) repurposing the double helix to probe, in real-time, excitation-contraction coupling in smooth muscle shortening; 3) developing ‘bronchi-chip’ that enables chemical and mechanical interrogation into heterotypic cell-to-cell communications; 4) discovering new therapeutic modalities to treat obstructive lung disease; 5) defining the physics of cancer cell migration and invasion; and 6) uncovering the ‘forbidden’ perceptions in metastatic spread of cancers.

 

Selected Publications:

  1. Molecular Nanomechanical Mapping of Histamine-Induced Smooth Muscle Cell Contraction and Shortening. Jo MH, Kim BC, Sung K, Panettieri RA Jr, An SS, Liu J, Ha T.ACS Nano. 2021 Jul 1. doi: 10.1021/acsnano.1c01782. Online ahead of print. PMID: 34197709
  2. Mechanical stress determines the configuration of TGFβ activation in articular cartilage. Zhen G, Guo Q, Li Y, Wu C, Zhu S, Wang R, Guo XE, Kim BC, Huang J, Hu Y, Dan Y, Wan M, Ha T, An S, Cao X. Nat Commun. 2021 Mar 17;12(1):1706. doi: 10.1038/s41467-021-21948-0. PMID: 33731712
  3. PGC1/PPAR drive cardiomyocyte maturation at single cell level via YAP1 and SF3B2. Murphy SA, Miyamoto M, Kervadec A, Kannan S, Tampakakis E, Kambhampati S, Lin BL, Paek S, Andersen P, Lee DI, Zhu R, An SS, Kass DA, Uosaki H, Colas AR, Kwon C. Nat Commun. 2021 Mar 12;12(1):1648. doi: 10.1038/s41467-021-21957-z. PMID: 33712605
  4. The odorant receptor OR2W3 on airway smooth muscle evokes bronchodilation via a cooperative chemosensory tradeoff between TMEM16A and CFTR. Huang J, Lam H, Koziol-White C, Limjunyawong N, Kim D, Kim N, Karmacharya N, Rajkumar P, Firer D, Dalesio NM, Jude J, Kurten RC, Pluznick JL, Deshpande DA, Penn RB, Liggett SB, Panettieri RA Jr, Dong X, An SS. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28485-28495. doi: 10.1073/pnas.2003111117. Epub 2020 Oct 23. PMID: 33097666
  5. A microphysiological model of the bronchial airways reveals the interplay of mechanical and biochemical signals in bronchospasm. Kilic O, Yoon A, Shah SR, Yong HM, Ruiz-Valls A, Chang H, Panettieri RA Jr, Liggett SB, Quiñones-Hinojosa A, An SS, Levchenko A. Nat Biomed Eng. 2019 Jul;3(7):532-544. doi: 10.1038/s41551-019-0366-7. Epub 2019 Mar 11. PMID: 31150010
  6. AIM1 is an actin-binding protein that suppresses cell migration and micrometastatic dissemination. Haffner MC, Esopi DM, Chaux A, Gürel M, Ghosh S, Vaghasia AM, Tsai H, Kim K, Castagna N, Lam H, Hicks J, Wyhs N, Biswal Shinohara D, Hurley PJ, Simons BW, Schaeffer EM, Lotan TL, Isaacs WB, Netto GJ, De Marzo AM, Nelson WG, An SS, Yegnasubramanian S. Nat Commun. 2017 Jul 26;8(1):142. doi: 10.1038/s41467-017-00084-8. PMID: 28747635
  7. Directed migration of cancer cells guided by the graded texture of the underlying matrix. Park J, Kim DH, Kim HN, Wang CJ, Kwak MK, Hur E, Suh KY, An SS, Levchenko A. Nat Mater. 2016 Jul;15(7):792-801. doi: 10.1038/nmat4586. Epub 2016 Mar 14. PMID: 26974411
  8. An inflammation-independent contraction mechanophenotype of airway smooth muscle in asthma. An SS, Mitzner W, Tang WY, Ahn K, Yoon AR, Huang J, Kilic O, Yong HM, Fahey JW, Kumar S, Biswal S, Holgate ST, Panettieri RA Jr, Solway J, Liggett SB. J Allergy Clin Immunol. 2016 Jul;138(1):294-297.e4. doi: 10.1016/j.jaci.2015.12.1315. Epub 2016 Feb 28. PMID: 26936804
  9. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB. Nat Med. 2010 Nov;16(11):1299-304. doi: 10.1038/nm.2237. Epub 2010 Oct 24. PMID: 20972434
  10. Universal physical responses to stretch in the living cell. Trepat X, Deng L, An SS, Navajas D, Tschumperlin DJ, Gerthoffer WT, Butler JP, Fredberg JJ. Nature. 2007 May 31;447(7144):592-5. doi: 10.1038/nature05824. PMID: 17538621