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Linderman Library Rotunda stained glass dome
 Damien Thévenin, professor of chemistry at Lehigh University

Damien Thévenin

Professor

Chair

610.758-2886
dat311@lehigh.edu
Seeley G. Mudd, Room 696
Education:

Ph.D. Chemistry & Biochemistry, University of Delaware (Newark, DE, USA)

M.S. Biology & Biotechnology, Université Paul Sabatier (Toulouse, France)

B.S. Structural Biochemistry, Université Paul Sabatier (Toulouse, France)

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Additional Interests

  • Membrane protein structure and function
  • Receptor Protein-Tyrosine Phosphatases
  • Targeted cancer therapy, drug delivery
  • Cell signaling
  • Transmembrane domain interaction
  • Therapeutic peptides design
  • System biology

Research Statement

Research in the Thévenin Lab lies at the intersection of chemistry, biophysics, and cell biology, with a specific emphasis on membrane protein cell signaling, protein-membrane interactions, and innovative cancer drug delivery strategies. Our group has established itself at the forefront of developing pH-sensitive peptides as targeted cancer therapies, particularly utilizing the pH (Low) Insertion Peptide (pHLIP) platform. Significant accomplishments include pioneering the application of pHLIP peptides to deliver therapeutic agents such as microtubule inhibitors, receptor-targeted peptides, and mitochondrial-disrupting agents selectively into tumor cells. Our research has also provided fundamental insights into the molecular determinants of pHLIP’s tumor selectivity, notably lipid composition and divalent cation influence.

Currently, we are advancing our therapeutic platforms through several ongoing projects. These include re-engaging the immune response to attack tumors using innovative peptide-based conjugates, enhancing therapeutic targeting through rational peptide design guided by machine learning, and expanding translational validation efforts into preclinical models. Concurrently, we are leveraging systems biology to understand better the effects of transmembrane (TM) domain-targeting peptides and mutations in Receptor Protein-Tyrosine Phosphatases (RPTPs), particularly PTPRJ, on cancer signaling pathways and cellular behaviors. Additionally, we are actively exploring structural dynamics of RPTP oligomerization and interactions within membranes through collaborations employing high-resolution NMR and cryo-electron microscopy.

Looking ahead, my group aims to bridge our therapeutic strategies from bench to bedside by translating these membrane-targeted platforms into clinical applications. We will further integrate mechanistic insights with advanced computational approaches, such as systems biology analyses and peptide design driven by generative diffusion models, to refine our understanding of fundamental biology and personalize therapeutic interventions. 

Biography

Prof. Thévenin was raised in the south of France, where he obtained his B.S. in Structural Biochemistry and M.S. in Biology and Biotechnology from Université Paul Sabatier in Toulouse, concentrating on engineering lipase catalysis in organic solvents. He completed his Ph.D. in Chemistry and Biochemistry at the University of Delaware, studying G-protein Coupled Receptors (GPCRs) folding and interaction. Choosing to maintain his focus on membrane protein structure and function, he conducted postdoctoral research at Yale University with Prof. Donald Engelman, investigating the effect of small-molecule drugs on the thrombopoietin receptor dimerization and the biophysical properties and anti-cancer therapeutic potential of the pH-Low Insertion Peptide (pHLIP). He subsequently joined Lehigh University to establish his independent research group, concentrating on interdisciplinary studies in cell biology, peptide chemistry, membrane protein biochemistry, and biophysics.

Selected Recent Publications

  • Sreeja S, Knepper L, Ankrom ET, Cucé G, Kong L, Ratajczak A, Im W, Thévenin D, and Honerkamp-Smith A*. (2024) Microfluidic Measurement of the Size and Shape of Lipid-Anchored Proteins. Biophysical Journal 123, 19: 3478–89. doi: 10.1016/j.bpj.2024.08.026.
  • Ankrom ET, Delassandro B, Pires MM, Thévenin D* (2024) Selective Recruitment of Antibodies to Cancer Cells and Immune Cell-mediated Killing via In Situ Click Chemistry. ChemMedChem, 19, e202400356. doi: 10.1002/cmdc.202400356.
  • Knepper L, Ankrom ET, and Thévenin D* (2024) “Enhancing Anti-Cancer Immune Response by Acidosis-Sensitive Nanobody Display.” The Journal of Membrane Biology, 257: 391–401. doi: 10.1007/s00232-024-00322-3.
  • Kelly JE, Ankrom ET, Newkirk SE, Thévenin D, Pires MM* (2024) Targeted Acidosis-Mediated Delivery of Antigenic MHC-Binding Peptides. Front. Immunol. 2024, 15. DOI:10.3389/fimmu.2024.1337973.
  • Rizzo S, Thévenin D* (2024) Identifying Transmembrane Interactions in Receptor Protein Tyrosine Phosphatase Homodimerization and Heterodimerization. In Protein Tyrosine Phosphatases, edited by Damien Thévenin and Jörg P. Müller, 2743:195–209. Methods in Molecular Biology. New York, NY: Springer US, 2024.
  • Gerritsen J, Rizzo S, Thévenin D, White F* (2024) Mass spectrometry-based analysis of receptor phosphatase effects on signaling networks. Methods Mol Biol.
  • Schwarz M, Rizzo S, Espinoza Paz W, Kresinsky A, Thévenin D, Müller JP (2022)  Disrupting PTPRJ Transmembrane-Mediated Oligomerization Counteracts Oncogenic Receptor Tyrosine Kinase FLT3 ITD.  Frontiers in Oncology, Vol 12. doi:10.3389/fonc.2022.1017947
  • Vasquez-Montes V,  Goldberg AFX*, Thévenin D*, Ladokhin AS* (2022) Ca2+ and Mg2+ Influence the Thermodynamics of Peptide-Membrane Interactions. Journal of Molecular Biology, 14;434(21):167826. doi:10.1016/j.jmb.2022.167826
  • Vasquez-Montes V, Tyagi V, Sikorski E, Kyrychenko A, Freites JA, Thévenin D*, Tobias DJ*, Ladokhin AS* (2022) Ca2+‐dependent interactions between lipids and the tumor‐targeting peptide pHLIP. Protein Science, 31( 9):e4385. doi:10.1002/pro.4385
  • Sikorski E, Wehr J, Ferraro NJ, Rizzo S, Pires MM, Thévenin D* (2022) Selective Display of a Chemoattractant Agonist on Cancer Cells Activates the Formyl Peptide Receptor 1 on Immune Cells. ChemBioChem (Online ahead of print). doi:10.1002/cbic.202100521.r
  • Sikorski E, Bloch E, Feigman MS, Ferraro NJ, Baybutt T, Snook AE, Pires MM, Thévenin D* (2020) pH-Dependent Grafting of Cancer Cells with Antigenic Epitopes Promotes Selective Antibody-Mediated Cytotoxicity. Journal of Medicinal Chemistry, 63(7): 3713-3722. doi:10.1021/acs.jmedchem.0c00016

Teaching

CHM 371: Elements of Biochemistry
CHM 336: Clinical Chemistry
CHM 362: Molecular Biophysics
CHM 465: Protein Separation & Biophysical Characterization