Description of Research Expertise:
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.
Chi-Chang Wang, Sean Carlin, Catherine Hou, Tyler Metz, Shihong Li, Hsiaoju Lee, Kuiying Xu, Mehran Makvandi, Robert H. Mach: Correlation analysis of [18F]ROStrace using ex vivo autoradiography and dihydroethidium fluorescent imaging in lipopolysaccharide-treated animals Biochem Biophys Res Comm 20 (516(2)): 397-401,2019.
Coenen Heinz H, Gee Antony D, Adam Michael, Antoni Gunnar, Cutler Cathy S, Fujibayashi Yasuhisa, Jeong Jae Min, Mach Robert H, Mindt Thomas L, Pike Victor W, Windhorst Albert D: Status of the 'consensus nomenclature rules in radiopharmaceutical sciences' initiative. Nuclear medicine and biology 71 : 19-22,2019.
Elmi Azadeh, Makvandi Mehran, Weng Chi-Chang, Hou Catherine, Clark Amy S, Mach Robert H, Mankoff David A: Cell-Proliferation Imaging for Monitoring Response to CDK4/6 Inhibition Combined with Endocrine-Therapy in Breast Cancer: Comparison of [F]FLT and [F]ISO-1 PET/CT. Clinical cancer research : an official journal of the American Association for Cancer Research 25 (10): 3063-3073,2019.
Reilly Sean W, Riad Aladdin A, Hsieh Chia-Ju, Sahlholm Kristoffer, Jacome Daniel A, Griffin Suzy, Taylor Michelle, Weng Chi-Chang, Xu Kuiying, Kirschner Nathan, Luedtke Robert R, Parry Christopher, Malhotra Shipra, Karanicolas John, Mach Robert H: Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D Receptor (DR) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs). Journal of medicinal chemistry 62 (10): 5132-5147,2019.
Makvandi Mehran, Lee Hwan, Puentes Laura N, Reilly Sean W, Rathi Komal S, Weng Chi-Chang, Chan Ho Sze, Hou Catherine, Raman Pichai, Martinez Daniel, Xu Kuiying, Carlin Sean D, Greenberg Roger A, Pawel Bruce R, Mach Robert H, Maris John M, Pryma Daniel A: Targeting PARP-1 with Alpha-Particles Is Potently Cytotoxic to Human Neuroblastoma in Preclinical Models. Molecular cancer therapeutics : 2019.
Reilly Sean W, Puentes Laura N, Schmitz Alexander, Hsieh Chia-Ju, Weng Chi-Chang, Hou Catherine, Li Shihong, Kuo Yin-Ming, Padakanti Prashanth, Lee Hsiaoju, Riad Aladdin A, Makvandi Mehran, Mach Robert H: Synthesis and evaluation of an AZD2461 [F]PET probe in non-human primates reveals the PARP-1 inhibitor to be non-blood-brain barrier penetrant. Bioorganic chemistry 83 : 242-249,2019.
Zeng Chenbo, Weng Chi-Chang, Schneider Mark E, Puentes Laura, Riad Aladdin, Xu Kuiying, Makvandi Mehran, Jin Linda, Hawkins William G, Mach Robert H: TMEM97 and PGRMC1 do not mediate sigma-2 ligand-induced cell death. Cell death discovery 5 : 58,2019.
Riad Aladdin, Zeng Chenbo, Weng Chi-Chang, Winters Harrison, Xu Kuiying, Makvandi Mehran, Metz Tyler, Carlin Sean, Mach Robert H: Sigma-2 Receptor/TMEM97 and PGRMC-1 Increase the Rate of Internalization of LDL by LDL Receptor through the Formation of a Ternary Complex. Scientific reports 8 (1): 16845,2018.
Powell Gregory L, Bonadonna John Paul, Vannan Annika, Xu Kuiying, Mach Robert H, Luedtke Robert R, Neisewander Janet L: Dopamine D3 receptor partial agonist LS-3-134 attenuates cocaine-motivated behaviors. Pharmacology, biochemistry, and behavior 175 : 123-129,2018.
Makvandi, M., Pantel, A., Schwartz, L., Schubert, E., Xu, K., Hsieh, C. J., Hou, C., Kim, H., Weng, C. C., Winters, H., Doot, R., Farwell, M. D., Pryma, D. A., Greenberg, R. A., Mankoff, D. A., Simpkins, F., Mach, R. H., Lin, L. L.: A PET imaging agent for evaluating PARP-1 expression in ovarian cancer J Clin Invest 128 (5): 2116-2126,2018.
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