Robert H Mach, Ph.D.

faculty photo
Britton Chance Professor of Radiology
Department: Radiology
Graduate Group Affiliations

Contact information
Department of Radiology
Vagelos Laboratory, Rm 1012
231 S. 34th Street
Philadelphia, PA 19104
Office: 215-746-8233
B.A. (Chemistry)
State University of New York, College at Potsdam, 1978.
Ph.D. (Medical Chemistry)
State University of New York at Buffalo, Buffalo, NY, 1985.
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Description of Research Expertise

Research Interests. Research in my lab is focused on development of radiotracers for studying the molecular basis of disease using the imaging technique, positron emission tomography or PET.

Keywords. Dopamine D3 receptors, alpha synuclein, PARP-1, neurodegeneration, addiction.

Research Details. My current research projects include the development of radiotracers for imaging: 1) dopamine D3 receptors in addiction; 2) alpha synuclein in Parkinson’s disease and other synucleinopathies; and 3) PARP-1 in cancer and CNS disorders. My laboratory is also studying cancer cell biology, and identified the role of a ternary complex between the sigma-2 receptor/TMEM97, LDL receptor, and progesterone receptor membrane component 1 (PGRMC1) in providing the high levels of cholesterol needed to support cell proliferation.

Rotation Projects. 1) In silico and computational chemistry methods for identifying small molecule - protein interactions. 2) Mechanism of receptor mediated internalization mediated by the TMEM97-sigma-2 receptor/PGRMC1 protein complex. 3) Molecular imaging of CNS receptors with PET.

Lab Personnel. The Mach lab currently has 1 graduate student, 3 postdoctoral research associates in cell biology, 3 postdoctoral research associates in chemistry and 5 support staff.

Selected Publications

Janssen B, Tian G, Lengyel-Zhand Z, Hsieh C-J, Loughee MG, Riad A, Xu K, Hou C, Weng C-C, Lopresti BJ, Kim HJ, Pagar VV, Ferrie JJ, Garcia BA, Mathis CA, Luk K, Petersson EJ, Mach RH: Identification of a putative -synuclein radioligand using an in silico similarity search. Molecular Imaging and Biology 25(4): 704-719, Aug 2023 Notes: DOI: 10.1007/s11307-023-01814-9.

Graham TJA, Lindberg A, Tong J, Stehouwer JS, Vasdev N, Mach RH, Mathis CA: In silico discovery and subsequent characterization of potent 4R-tauopathy Positron Emission Tomography radiotracers. J. Med. Chem Jul 2023 Notes: DOI: 10.1021/acs.jmedchem.3c00775 Online ahead of print.

Han QJ, Forfia P, Vaidya A, Ramani G, deKemp RA, Mach RH, Mankoff DA, Bravo PE, DiCarli M, Chan SY, Waxman AB, Han Y: Effects of ranolazine on right ventricular function, fluid dynamics, and metabolism in patients with precapillary pulmonary hypertension: insights from a longitudinal, randomized, double-blind, placebo controlled, multicenter study. Front Cardiovasc Med 10: 1118796, Jun 2023 Notes: DOI: 10.3389/fcvm.2023.1118796.

Cory MB, Jones CM, Shaffer KD, Venkatesh Y, Giannakoulias S, Perez RM, Lougee MG, Hummingbird E, Pagar VV, Hurley CM, Li A, Mach RH, Kohli RM, Petersson EJ: FRETing about the details: Case studies in the use of a genetically encoded fluorescent amino acid for distance-dependent energy transfer. Protein Sci 32(5): e4633, May 2023 Notes: DOI: 10.1002/pro.4633.

Wetherill RR, Doot RK, Young AJ, Lee H, Schubert EK, Wiers CE, Leone FT, Mach RH, Kranzler HR, Dubroff JG: Molecular imaging of pulmonary inflammation in electronic and combustible cigarette users: a pilot study. J. Nucl. Med 64(5): 797-802, May 2023 Notes: DOI: 10.2967/jnumed.122.264529.

Estrada-Sanchez AM, Rangel-Barajas C, Howe AG, Barton SJ, Mach RH, Luedtke RR, Rebec GV: Selective activation of D3 dopamine receptors ameliorates DOI-induced head twitching accompanied by changes in corticostriatal processing. Int J Mol Sci 24(11): 9300, May 2023 Notes: DOI: 10.3390/ijms24119300.

Pantel AR, Gitto SB, Makvandi M, Kim H, Medvedv S, Weeks J, Torigian D, Hsieh C-J, Ferman B, Latif N, Tanyi J, Martin L, Lanzo S, Liu F, Cao Q, Mills G, Doot R, Mankoff D, Mach RH, Lin L, Simpkins F: [18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a pilot study. Clinical Cancer Research 29(8): 1515-1527, Apr 2023 Notes: DOI: 10.1158/1078-0432.CCR-22-1602.

Gao R-D, Taylor M, McInnis T, Chen Z, Gori SS, LaPorte HM, Siegler MA, Neisewander JL, Mach RH, Singh M, Slusher BS, Rais R, Luedtke RR, Tsakamoto T: Synthesis and pharmacological characterization of a difluorinated analog of reduced haloperidol as a sigma-1 ligand. ACS. Chem. Neurosci 14(5): 947-957, Mar 2023 Notes: DOI: 10.1021/acschemneuro.2c00791.

Hsieh C-J, Giannakoulias S, Petersson EJ, Mach RH: Computational chemistry for the identification of lead compounds for radiotracer development. Pharmaceuticals 16(2): 317, Feb 2023 Notes: DOI: 10.3390/ph16020317.

Thejer BM, Infantino V, Santarsiero A, Pappalardo I, Abatematteo FS, Teakel S, Van Oosterum AV, Mach RH, Denora N, Lee BC, Resta N, Bagnulo R, Niso M, Contino M, Montsch B, Heffeter P, Cahill MA, Abate C: Evidence for functional association between TSPO and TMEM97 regulated by sigma-2 receptor ligand binding in MCF7 and MIA PaCa-2 cells. Int. J. Mol. Sci Page: 6381, 2023.

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Last updated: 08/09/2023
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