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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. 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. My group was also the first to develop PET radiotracers that have been used in the following molecular imaging studies: 1) increased expression of inducible nitric oxide synthase (iNOS) in heart transplant patients at risk for transplant rejection; 2) sigma-2 receptors as a biomarker for imaging the proliferative status of solid tumors; 3) caspase-3 activation in tissues undergoing caspase-mediated apoptosis; 4) increased PARP-1 levels in ovarian and breast cancer patients as a predictor of response to PARP inhibitors; and 5) imaging superoxide levels as a molecular marker of proinflammatory microglial activation in neuroinflammation.
263., Ferrie JJ, Lengyel-Zhand, Z, Janssen B, Lougee MG, Giannakoulias S, Hsieh C-J, Pagar VV, Weng C-C, Xu H, Graham TJA, Lee VM-Y, Mach RH, Petersson EJ: Identification of a nanomolar affinity a-synuclein fibril imaging probe by ultra-high throughput in silico screening Chem Sci In Press : 2020.
Sellmyer MA, Richman SA, Lohith K, Hou C, Weng CC, Mach RH, O'Connor RS, Milone MC, Farwell MD: Imaging CAR T Cell Trafficking with eDHFR as a PET Reporter Gene. Molecular Therapy 28 : 2020.
Ågren R, Zeberg H, Maciej Stępniewski T, Free RB, Reilly SW, Luedtke RR, Århem P, Ciruela F, Sibley DR, Mach RH, Selent J, Nilsson J, Sahlholm K: A ligand with two modes of interaction with the dopamine D2 receptor- an induced-fit mechanism of insurmountable antagonism ACS Chem Neurosci Online : 2020.
Zeng C, Riad A, Mach RH: The biological function of sigma-2/TMEM97 and its utility in PET imaging studies in cancer Cancers 12 : 2020.
Riad A, Lengyel-Zhand Z, Zeng C, Weng C-C, Lee VMY, Trojanowski JQ, Mach RH: The Sigma-2 Receptor/TMEM97, PGRMC1, and LDL Receptor complex are responsible for the cellular uptake of Aβ42 and its protein aggregates Mol Neurobiol 57 : 2020.
Lee H, Riad A, Martorano P, Mansfield A, Samanta M, Batra V, Mach RH, Maris JM, Pryma DA, Makvandi M: PARP-1-targeted Auger emitters display high-LET cytotoxic properties in vitro but show limited therapeutic utility in solid tumor models of human neuroblastoma. J Nucl Med 61 : 2020.
McDonald ES, Doot RK, Pantel AR, Farwell MD, Mach RH, Maxwell KN, Mankoff DA: Positron Emission Tomography Imaging of Poly-(Adenosine Diphosphate-Ribose) Polymerase 1 Expression in Breast Cancer: A Nonrandomized Clinical Trial JAMA Oncol 6 : 2020.
Lengyel-Zhand Z, Ferrie JJ, Janssen B, Hsieh CJ, Graham T, Xu KY, Haney CM, Lee VM, Trojanowski JQ, Petersson EJ, Mach RH: Synthesis and characterization of high affinity fluorogenic α-synuclein probes. Chem Communications 56 : 2020.
McDonald ES, Doot RK, Young AJ, Schubert EK, Pryma DA, Farwell MD, Tchou J, Nayak A, Ziober A, Feldman MD, DeMichele A, Clark AS, Shah PD, Lee H, Carlin SD, Mach RH, Mankoff DA: Breast cancer 18F-ISO-1 uptake as a marker of proliferation status. J Nucl Med 61 : 2020.
Ellison PA, Olson AP, Barnhart TE, Hoffman SLV, Reilly SW, Makvandi M, Bartels JL, Murali D, DeJesus OT, Lapi SE, Bednarz B, Nickles RJ, Mach RH, Engle JW: Improved production of 76Br, 77Br and 80mBr via CoSe cyclotron targets and vertical dry distillation. Nucl Med Biol 81 : 2020.
Department of RadiologyVagelos Laboratory, Rm 1010231 S. 34th Street