Mark R. Spaller, PhD
Associate Professor of Medical Education
Associate Professor of Chemistry (Adjunct)
Norris Cotton Cancer Center
Program in Experimental and Molecular Medicine
7936 Rubin 652
Dartmouth-Hitchcock Medical Center
One Medical Center Drive
Lebanon NH 03756
Office: Rubin 652
Discovery and development of cellular probes and therapeutic agents targeting protein-protein interactions; chemical biology; peptide and organic small molecule design and synthesis; chemical libraries for biochemical and cell-based screening; protein biochemistry and biophysical analysis of protein-ligand interactions.
Rotations and Thesis Projects:
Rotation and thesis projects are available that correspond to the topics listed above under “Professional Interests”. These are applicable to the study of diseases involving cancer, neurobiological disorders, and bacterial infection.
Mark Spaller is currently Associate Professor of Medical Education at the Geisel School of Medicine, and Associate Professor (Adjunct) of Chemistry and Biological Sciences at Dartmouth College. He completed his doctoral studies at the University of Texas at Austin, where he conducted research in the fields of synthetic organic chemistry and protein biochemistry. This was followed by a move to the University of California, Berkeley, where he served as an American Cancer Society postdoctoral fellow, devising new synthetic methods for use in preparing chemical libraries for drug discovery screens. He began his independent academic career at Wayne State University, as a member of the biochemistry division in the Department of Chemistry, where he first immersed himself as a teacher of full-term classes in both the undergraduate and graduate programs. During this period, he also established an NIH-funded research laboratory that focused on the development of peptides and proteins for use as biochemical and biological tools in basic and translational applications. He subsequently moved to Brown University, and then again in 2008 to Dartmouth. Prof. Spaller is course director for Pharmacology for second-year medical students in Geisel, and also teaches both in the graduate and undergraduate curriculum, the latter within the College’s departments of Biological Sciences and Chemistry, as a member of the Arts & Sciences faculty. In addition, Prof. Spaller directs an independent research laboratory within the Norris Cotton Cancer Center, which explores the use of small molecules, peptides and proteins in biomedical applications, and which has developed a number of collaborative partnerships with other research laboratories within and outside Dartmouth College.
Saro D, Li T, Rupasinghe C, Paredes A, Caspers N, Spaller MR. A thermodynamic ligand binding study of the third PDZ domain (PDZ3) from the mammalian neuronal protein PSD-95. Biochemistry. 2007 May 29;46(21):6340-52. (view details on MedLine)
Knafo S, et al. PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Nat Neurosci. 2016 Mar;19(3):443-53 (view details on MedLine)
Udugamasooriya DG, Spaller MR. Conformational constraint in protein ligand design and the inconsistency of binding entropy. Biopolymers. 2008 Aug;89(8):653-67. (view details on MedLine)
Marshall J, Wong KY, Rupasinghe CN, Tiwari R, Zhao X, Berberoglu ED, Sinkler C, Liu J, Lee I, Parang K, Spaller MR, Hüttemann M, Goebel DJ Inhibition of N-methyl-D-aspartate-induced retinal neuronal death by polyarginine peptides Is linked to the attenuation of stress-induced hyperpolarization of the inner mitochondrial membrane potential. J Biol Chem. 2015 Sep 4;290(36):22030-48. (view details on MedLine)
Udugamasooriya DG, Sharma SC, Spaller MR. A chemical library approach to organic-modified peptide ligands for PDZ domain proteins: a synthetic, thermodynamic and structural investigation. Chembiochem. 2008 Jul 2;9(10):1587-9. (view details on MedLine)
Memic A, Spaller MR. How do halogen substituents contribute to protein-binding interactions? A thermodynamic study of peptide ligands with diverse aryl halides. Chembiochem. 2008 Nov 24;9(17):2793-5. (view details on MedLine)
Muders MH, Vohra PK, Dutta SK, Wang E, Ikeda Y, Wang L, Udugamasooriya DG, Memic A, Rupasinghe CN, Baretton GB, Aust DE, Langer S, Datta K, Simons M, Spaller MR, Mukhopadhyay D. Targeting GIPC/synectin in pancreatic cancer inhibits tumor growth. Clin Cancer Res. 2009 Jun 15;15(12):4095-103. (view details on MedLine)
LeBlanc BW, Iwata M, Mallon AP, Rupasinghe CN, Goebel DJ, Marshall J, Spaller MR, Saab CY. A cyclic peptide targeted against PSD-95 blocks central sensitization and attenuates thermal hyperalgesia. Neuroscience. 2010 May 5;167(2):490-500. (view details on MedLine)
Wang L, Lau JS, Patra CR, Cao Y, Bhattacharya S, Dutta S, Nandy D, Wang E, Rupasinghe CN, Vohra P, Spaller MR, Mukhopadhyay D. RGS-GAIP-interacting protein controls breast cancer progression. Mol Cancer Res. 2010 Dec;8(12):1591-600. (view details on MedLine)
Patra CR, Rupasinghe CN, Dutta SK, Bhattacharya S, Wang E, Spaller MR, Mukhopadhyay D. Chemically modified peptides targeting the PDZ domain of GIPC as a therapeutic approach for cancer. ACS Chem Biol. 2012 Apr 20;7(4):770-9. (view details on MedLine)