Gregory Thatcher

Greg Thatcher, PhD, joined the University of Arizona in 2020 from the University of Illinois College of Pharmacy. In his career, he has graduated over 50 students with PhD’s and a dozen with MSc’s and mentored 40 undergraduate researchers, the majority while on faculty in the Chemistry Department at Queen's University in Canada from 1988 until 2002. These trainees have proceeded to positions in biotech, pharma, business, education, and academia in the USA, Canada, Europe, India, and China.

While at the University of Illinois in Chicago (UIC), Thatcher acted as founder/leader of the Translational Oncology Program in the University of Illinois Cancer Center and co-director of the NIA Predoctoral Training Program in Alzheimer’s Disease & Related Dementia. In 2013, he founded a campus-wide and disease-agnostic drug discovery center at UIC, focused on small molecule drug discovery, which continues to play an active role in academic drug discovery across Chicago. Dr. Thatcher created his first start-up biotech company in 1997, which successfully took an Alzheimer’s drugs into human clinical trials. Thatcher’s trainees receive a multidisciplinary education in modern aspects of medicinal chemistry, chemical biology, and chemical toxicology: the underpinning of drug discovery and development. Students who graduate with expertise in synthetic medicinal chemistry will have competency in another area, such as drug metabolism and pharmacokinetics; and students who graduate with expertise in cell/molecular biology or biochemistry will be experts in bioassay design and have competency in drug discovery.

The Thatcher lab’s research has been continuously funded by the NIH since 2003, supported by NCI, NIA, NHLBI, NIAID, and NCCAM, resulting in over 170 publications and dozens of issued patents. Two new chemical entities were licensed and successfully completed Phase 1 clinical trials for metastatic breast cancer in 2019. The first five publications listed below describe drugs that have completed Phase 1 trials:

1. Dudek, A. Z., Liu, L. C., Fischer, J. H., Wiley, E. L., Sachdev, J. C., Bleeker, J., Hurley, R. W., Tonetti, D. A., Thatcher, G. R. J., Venuti, R. P., and O'Regan, R. M. (2020) Phase 1 study of TTC-352 in patients with metastatic breast cancer progressing on endocrine and CDK4/6 inhibitor therapy, Breast Cancer Res Treat 183, 617-627. 
2. Andreano, K. J., Wardell, S. E., Baker, J. G., Desautels, T. K., Baldi, R., Chao, C. A., Heetderks, K. A., Bae, Y., Xiong, R., Tonetti, D. A., Gutgesell, L. M., Zhao, J., Sorrentino, J. A., Thompson, D. A., Bisi, J. E., Strum, J. C., Thatcher, G. R. J., and Norris, J. D. (2020) G1T48, an oral selective estrogen receptor degrader, and the CDK4/6 inhibitor lerociclib inhibit tumor growth in animal models of endocrine-resistant breast cancer, Breast Cancer Res Treat 180, 635-646. 
3. Xiong, R., Zhao, J., Gutgesell, L. M., Wang, Y., Lee, S., Karumudi, B., Zhao, H., Lu, Y., Tonetti, D. A., and Thatcher, G. R. (2017) Novel Selective Estrogen Receptor Downregulators (SERDs) Developed against Treatment-Resistant Breast Cancer, J Med Chem 60, 1325-1342.   
4. Xiong, R., Patel, H. K., Gutgesell, L. M., Zhao, J., Delgado-Rivera, L., Pham, T. N. D., Zhao, H., Carlson, K., Martin, T., Katzenellenbogen, J. A., Moore, T. W., Tonetti, D. A., and Thatcher, G. R. J. (2016) Selective Human Estrogen Receptor Partial Agonists (ShERPAs) for Tamoxifen-Resistant Breast Cancer, J Med Chem 59, 219-237.
5. Luo, J., Lee, S. H., VandeVrede, L., Qin, Z., Piyankarage, S., Tavassoli, E., Asghodom, R. T., Ben Aissa, M., Fa, M., Arancio, O., Yue, L., Pepperberg, D. R., and Thatcher, G. R. (2015) Re-engineering a neuroprotective, clinical drug as a procognitive agent with high in vivo potency and with GABAA potentiating activity for use in dementia, BMC Neurosci 16, 67.

Research Projects

Although the Thatcher lab's greatest success has been in breast cancer; we have an opportunity to prioritize diseases of aging at UA, in particular Alzheimer’s and Related Dementia (ADRD), which is currently funded by three National Institute on Aging grants. We are also able to pivot rapidly towards health crises, such as COVID-19 (see section 8 below).

In 1997 I founded a start-up with pharmacologists at Queen’s University in Canada, initially focused on small molecule neuroprotective therapeutics for ischemic stroke. This company succeeded in completing Phase 1A clinical trials in Alzheimer’s disease (AD) for a small molecule nomethiazole. This project derived from a long-standing interest in understanding the biological chemistry of nitric oxide as a basis for delivering NO in various disease states. The aim of restoring NO/cGMP/CREB signaling in the AD brain, a concept originally conceived by us, is now widely accepted. We maintain significant interest in AD addressing multiple targets in what is a multifactorial disease.  Another AD project targeted at calpain inhibitors has evolved to a focus on protecting the blood brain barrier, both activating CREB and increasing endothelial NO synthase (eNOS) may be crucial.

1. Luo, J., Lee, S. H., VandeVrede, L., Qin, Z., Ben Aissa, M., Larson, J., Teich, A. F., Arancio, O., D'Souza, Y., Elharram, A., Koster, K., Tai, L. M., LaDu, M. J., Bennett, B. M., and Thatcher, G. R. (2016) A multifunctional therapeutic approach to disease modification in multiple familial mouse models and a novel sporadic model of Alzheimer's disease, Mol Neurodegener 11, 35.
2. Hollas, M. A., Ben Aissa, M., Lee, S. H., Gordon-Blake, J. M., and Thatcher, G. R. J. (2019) Pharmacological manipulation of cGMP and NO/cGMP in CNS drug discovery, Nitric Oxide 82, 59-74.
3. Schiefer, I. T., Vandevrede, L., Fa, M., Arancio, O., and Thatcher, G. R. (2012) Furoxans (1,2,5-Oxadiazole-N-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents, J Med Chem 55, 3076-3087.
4. Vandevrede, L., Tavassoli, E., Luo, J., Qin, Z., Yue, L., Pepperberg, D. R., and Thatcher, G. R. J. (2014) Novel analogues of chlormethiazole are neuroprotective in four cellular models of neurodegeneration by a mechanism with variable dependence on GABAA receptor potentiation, Br J Pharmacol 171, 389-402.
5. Qin, Z., Luo, J., VandeVrede, L., Tavassoli, E., Fa, M., Teich, A. F., Arancio, O., and Thatcher, G. R. (2012) Design and synthesis of neuroprotective methylthiazoles and modification as NO-chimeras for neurodegenerative therapy, J Med Chem 55, 6784-6801.
6. Jastaniah, A., Gaisina, I. N., Knopp, R., and Thatcher, G. R. (2020) Synthesis of alpha-Ketoamide-based Stereoselective Calpain-1 Inhibitors as Neuroprotective Agents, ChemMedChem.
7. Fa, M., Zhang, H., Staniszewski, A., Saeed, F., Shen, L. W., Schiefer, I. T., Siklos, M. I., Tapadar, S., Litosh, V. A., Libien, J., Petukhov, P. A., Teich, A. F., Thatcher, G. R., and Arancio, O. (2015) Novel Selective Calpain 1 Inhibitors as Potential Therapeutics in Alzheimer's Disease, J Alzheimers Dis 49, 707-721.

We are currently targeting a domain of tau protein that is linked to pathogenesis of AD and other tauopathies, such as frontotemporal lobe dementia. Tau forms tangles that are one of the two hallmark pathologies of AD. In general, our AD research is not focused on AD pathology, since postmortem brains show individuals with severe pathology but no cognitive deficits at time of death. The concept of weakened neural reserve or cognitive resilience being necessary for an individual to decline to dementia, independent of pathology, has been proposed by collaborators. The contribution of traumatic brain injury (TBI) to loss of cognitive resilience with aging has also been proposed. In unpublished work, we have developed small molecule activators of the enzyme NAMPT that increase cellular NAD that is depleted with aging. We have also developed small molecules that restore cholesterol mobilization and insulin signaling, and attenuate inflammation and lipogenesis, in part by acting as LXRβ agonists. This approach is linked to addressing the major genetic risk factor for AD, which is the apolipoprotein APOE4.

1. Yu, L., Tasaki, S., Schneider, J. A., Arfanakis, K., Duong, D. M., Wingo, A. P., Wingo, T. S., Kearns, N., Thatcher, G. R. J., Seyfried, N. T., Levey, A. I., De Jager, P. L., and Bennett, D. A. (2020) Cortical Proteins Associated With Cognitive Resilience in Community-Dwelling Older Persons, JAMA Psychiatry.
2. Knopp, R. C., Lee, S. H., Hollas, M., Nepomuceno, E., Gonzalez, D., Tam, K., Aamir, D., Wang, Y., Pierce, E., BenAissa, M., and Thatcher, G. R. J. (2020) Interaction of oxidative stress and neurotrauma in ALDH2(-/-) mice causes significant and persistent behavioral and pro-inflammatory effects in a tractable model of mild traumatic brain injury, Redox Biol 32, 101486.
3. Gaisina, I. N., Lee, S. H., Kaidery, N. A., Ben Aissa, M., Ahuja, M., Smirnova, N. N., Wakade, S., Gaisin, A., Bourassa, M. W., Ratan, R. R., Nikulin, S. V., Poloznikov, A. A., Thomas, B., Thatcher, G. R. J., and Gazaryan, I. G. (2018) Activation of Nrf2 and Hypoxic Adaptive Response Contribute to Neuroprotection Elicited by Phenylhydroxamic Acid Selective HDAC6 Inhibitors, ACS Chem Neurosci 9, 894-900.
4. Tai, L. M., Koster, K. P., Luo, J., Lee, S. H., Wang, Y. T., Collins, N. C., Ben Aissa, M., Thatcher, G. R., and LaDu, M. J. (2014) Amyloid-beta pathology and APOE genotype modulate retinoid X receptor agonist activity in vivo, J Biol Chem 289, 30538-30555

In addition to APOE4 risk, women are at greater risk of AD; the exact cause is unknown, but there are extensive studies on the link between menopause, leading to loss of circulating estrogens, and AD. Breast cancer therapy usually involves chemical or surgical menopause and epidemiology has looked at the risk of dementia, although insomnia is a confounding factor. Definitively, women who undergo early oophorectomy have a significantly increased risk of dementia in later life. In our collaborations with the late, great Judy Bolton, we explored estrogen replacement therapy (ERT) and selective estrogen receptor (ER) modulators (SERMs) extensively, both from the perspective of risk/benefit balance associated with ERT and the pursuit on an “ideal SERM” that might provide a safer alternative to ERT. Currently a brain-bioavailable selective human ER partial agonist (ShERPA) is being studied in familial AD transgenic (FAD-Tg) mice that express human apoE isoforms.

1. Bolton, J. L., and Thatcher, G. R. J. (2008) Potential mechanisms of estrogen quinone carcinogenesis, Chem Res Toxicol 21, 93-101.
2. Yu, B., Dietz, B. M., Dunlap, T., Kastrati, I., Lantvit, D. D., Overk, C. R., Yao, P., Qin, Z., Bolton, J. L., and Thatcher, G. R. J. (2007) Structural modulation of reactivity/activity in design of improved benzothiophene selective estrogen receptor modulators: induction of chemopreventive mechanisms, Mol Cancer Ther 6, 2418-2428.  
3. Qin, Z., Kastrati, I., Ashgodom, R. T., Lantvit, D. D., Overk, C. R., Choi, Y., van Breemen, R. B., Bolton, J. L., and Thatcher, G. R. J. (2009) Structural modulation of oxidative metabolism in design of improved benzothiophene selective estrogen receptor modulators, Drug Metab Dispos 37, 161-169.
4. Hemachandra, L. P., Patel, H., Chandrasena, R. E., Choi, J., Piyankarage, S. C., Wang, S., Wang, Y., Thayer, E. N., Scism, R. A., Michalsen, B. T., Xiong, R., Siklos, M. I., Bolton, J. L., and Thatcher, G. R. J. (2014) SERMs attenuate estrogen-induced malignant transformation of human mammary epithelial cells by upregulating detoxification of oxidative metabolites, Cancer Prev Res (Phila) 7, 505-515.
5. VandeVrede, L., Abdelhamid, R., Qin, Z., Choi, J., Piyankarage, S., Luo, J., Larson, J., Bennett, B. M., and Thatcher, G. R. (2013) An NO donor approach to neuroprotective and procognitive estrogen therapy overcomes loss of NO synthase function and potentially thrombotic risk, PLoS One 8, e70740.

As part of the Bolton/Thatcher collaboration, we established significant literature in design, synthesis, mechanism, and metabolism of ER modulators, notably benzothiophene ligands related to raloxifene. This unique and holistic understanding is now permitting us to design novel ligands for estrogen receptors (ER), which are capable of tissue selective partial agonism, antagonism, and degradation (SERDs and PROTACs). We pursued these ligands as breast cancer therapeutics. Although ER+ breast cancer is well treated with endocrine therapy and increasing classes of targeted therapeutic agents, resistance to therapy occurs in more than half of patients, leading to metastatic disease: the majority of breast cancer victims have ER+ disease. Two distinct therapeutic approaches, have led to drugs from our labs completing clinical trials, a ShERPA and a selective ER degrader (SERD). A brain-SERD (BSERD) is poised for IND studies to treat breast cancer patients with brain metastases who have very poor prognosis and no targeted therapies.

1. Lu, Y., Gutgesell, L. M., Xiong, R., Zhao, J., Li, Y., Rosales, C. I., Hollas, M., Shen, Z., Gordon-Blake, J., Dye, K., Wang, Y., Lee, S., Chen, H., He, D., Dubrovyskyii, O., Zhao, H., Huang, F., Lasek, A. W., Tonetti, D. A., and Thatcher, G. R. J. (2019) Design and Synthesis of Basic Selective Estrogen Receptor Degraders for Endocrine Therapy Resistant Breast Cancer, J Med Chem 62, 11301-11323.
2. Molloy, M. E., White, B. E., Gherezghiher, T., Michalsen, B. T., Xiong, R., Patel, H., Zhao, H., Maximov, P. Y., Jordan, V. C., Thatcher, G. R.J., and Tonetti, D. A. (2014) Novel selective estrogen mimics for the treatment of tamoxifen-resistant breast cancer, Mol Cancer Ther 13, 2515-2526.
3. Abderrahman, B., Maximov, P. Y., Curpan, R. F., Hanspal, J. S., Fan, P., Xiong, R., Tonetti, D. A., Thatcher, G. R. J., and Jordan, V. C. (2020) Pharmacology and Molecular Mechanisms of Clinically Relevant Estrogen Estetrol and Estrogen Mimic BMI-135 for the Treatment of Endocrine-Resistant Breast Cancer, Mol Pharmacol 98, 364-381.

The development of SERDs, B-SERDs, and ShERPAs was driven by breast cancer cell lines resistant to endocrine therapy and resistant to the newer targeted therapeutics, fulvestrant and Cdk4/6 inhibitors (e.g. Palbociclib). All our work uses drug-resistant cell lines in order to find treatments for metastatic breast cancer. Since BET bromodomain proteins enhance the transcriptional effects of ER, BET inhibitors were developed to treat these resistant tumors. BET proteins are epigenetic readers binding to acetylated histones to stabilize transcriptional complexes at DNA. Our BET inhibitors have proven most impressive in combination with checkpoint inhibitors in pancreatic cancer and in non-cancer indications, such as fibrosis (both unpublished). Both the effects in pancreatic cancer and firbrosis derive from regulation of the immune response. Other immune-oncology projects are approaching the role of MLK3 and other kinases in T-cell activation and sensitization to checkpoint inhibitors; aiming for a dual kinase inhibitor for therapy of solid tumors.

1. Li, Y., Zhao, J., Gutgesell, L. M., Shen, Z., Ratia, K., Dye, K., Dubrovskyi, O., Zhao, H., Huang, F., Tonetti, D. A., Thatcher, G. R. J., and Xiong, R. (2020) Novel Pyrrolopyridone Bromodomain and Extra-Terminal Motif (BET) Inhibitors Effective in Endocrine-Resistant ER+ Breast Cancer with Acquired Resistance to Fulvestrant and Palbociclib, J Med Chem 63, 7186-7210.
2. Patel, H. K., Siklos, M. I., Abdelkarim, H., Mendonca, E. L., Vaidya, A., Petukhov, P. A., and Thatcher, G. R. (2014) A chimeric SERM-Histone deacetylase inhibitor approach to breast cancer therapy, ChemMedChem 9, 602-613.
3. Kastrati, I., Siklos, M. I., Brovkovych, S. D., Thatcher, G. R. J., and Frasor, J. (2017) A Novel Strategy to Co-target Estrogen Receptor and Nuclear Factor kappaB Pathways with Hybrid Drugs for Breast Cancer Therapy, Horm Cancer 8, 135-142.
4. Kastrati, I., Litosh, V. A., Zhao, S., Alvarez, M., Thatcher, G. R. J., and Frasor, J. (2015) A novel aspirin prodrug inhibits NFkappaB activity and breast cancer stem cell properties, BMC Cancer 15, 845.
5. Kumar, S., Singh, S. K., Viswakarma, N., Sondarva, G., Nair, R. S., Sethupathi, P., Sinha, S. C., Emmadi, R., Hoskins, K., Danciu, O., Thatcher, G. R. J., Rana, B., and Rana, A. (2020) Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity, Proc Natl Acad Sci U S A 117, 7961-7970.
6. Kumar, S., Singh, S. K., Viswakarma, N., Sondarva, G., Nair, R. S., Sethupathi, P., Dorman, M., Sinha, S. C., Hoskins, K., Thatcher, G., Rana, B., and Rana, A. (2020) Rationalized inhibition of mixed lineage kinase 3 and CD70 enhances life span and antitumor efficacy of CD8(+) T cells, J Immunother Cancer 8.

Estradiol and several SERMs undergo oxidative metabolism to generate quinones that may redox cycle and covalently modify biomolecules, which may contribute to the risk associated with ERT. Chemical carcinogenesis caused by exposure to estrogen oxidative metabolites from menarch to menopause is believed to be linked to breast cancer. The SERM tamoxifen undergoes Phase 1 and Phase 2 metabolism to yield an electrophile that reacts with DNA and may be the cause of uterine cancer risk associated with tamoxifen. Consequently, we have had a strong interest in protein covalent modification and its potential in enzyme inhibition and also to induce toxicity.

1. Peng, K. W., Wang, H., Qin, Z., Wijewickrama, G. T., Lu, M., Wang, Z., Bolton, J. L., and Thatcher, G. R. (2009) Selective estrogen receptor modulator delivery of quinone warheads to DNA triggering apoptosis in breast cancer cells, ACS Chem Biol 4, 1039-1049.
2. Wang, Z., Wijewickrama, G. T., Peng, K. W., Dietz, B. M., Yuan, L., van Breemen, R. B., Bolton, J. L., and Thatcher, G. R. J. (2009) Estrogen Receptor {alpha} Enhances the Rate of Oxidative DNA Damage by Targeting an Equine Estrogen Catechol Metabolite to the Nucleus, J Biol Chem 284, 8633-8642.
3. Pierce, E. N., Piyankarage, S. C., Dunlap, T., Litosh, V., Siklos, M. I., Wang, Y. T., and Thatcher, G. R. J. (2016) Prodrugs Bioactivated to Quinones Target NF-kappaB and Multiple Protein Networks: Identification of the Quinonome, Chem Res Toxicol 29, 1151-1159.
4. Kastrati, I., Siklos, M. I., Calderon-Gierszal, E. L., El-Shennawy, L., Georgieva, G., Thayer, E. N., Thatcher, G. R., and Frasor, J. (2016) Dimethyl Fumarate Inhibits the Nuclear Factor kappaB Pathway in Breast Cancer Cells by Covalent Modification of p65 Protein, J Biol Chem 291, 3639-3647.
5. Liu, J., Li, Q., Yang, X., van Breemen, R. B., Bolton, J. L., and Thatcher, G. R. J. (2005) Analysis of protein covalent modification by xenobiotics using a covert oxidatively activated tag: raloxifene proof-of-principle study, Chem Res Toxicol 18, 1485-1496.
6. Silvestri, I., Lyu, H., Fata, F., Banta, P. R., Mattei, B., Ippoliti, R., Bellelli, A., Pitari, G., Ardini, M., Petukhova, V., Thatcher, G. R. J., Petukhov, P. A., Williams, D. L., and Angelucci, F. (2020) Ectopic suicide inhibition of thioredoxin glutathione reductase, Free Radic Biol Med 147, 200-211.

Our early research made significant contributions in the physical organic and biological chemistry of phosphorylation reactions, a reaction central to post-translational modification (PTM). The application of this expertise to reactions underpinning chemical biology has been used in studying PTMs and covalent modification by NO, H2S, RSNO, and xenobiotics and their metabolites.  Work on NO and “nitrosylation” has challenged dogma. We have developed new chemoproteomics approaches to study cysteome PTMs to enable these studies. In addition, our expertise in protein covalent modification provides knowledge of mechanism of action required to design safer drugs.

1. Sinha, V., Wijewickrama, G. T., Chandrasena, R. E., Xu, H., Edirisinghe, P. D., Schiefer, I. T., and Thatcher, G. R. J. (2010) Proteomic and mass spectroscopic quantitation of protein S-nitrosation differentiates NO-donors, ACS Chem Biol 5, 667-680.
2. Wang, Y. T., Piyankarage, S. C., Williams, D. L., and Thatcher, G. R. J. (2014) Proteomic profiling of nitrosative stress: protein s-oxidation accompanies s-nitrosylation, ACS Chem Biol 9, 821-830.
3. Wang, Y.-T., Piyankarage, S. C., and Thatcher, G. R. J. (2016) Quantitative Profiling of Reversible Cysteome Modification Under Nitrosative Stress, in Neuromethods, pp 1-18, Humana Press, Totowa, NJ.
4. Yao, Y., Delgado-Rivera, L., Samareh Afsari, H., Yin, L., Thatcher, G. R. J., Moore, T. W., and Miller, L. W. (2018) Time-Gated Luminescence Detection of Enzymatically Produced Hydrogen Sulfide: Design, Synthesis, and Application of a Lanthanide-Based Probe, Inorg Chem 57, 681-688.
5. Yao, Y., Kong, C., Yin, L., Jain, A. D., Ratia, K., Thatcher, G. R., Moore, T. W., Driver, T. G., and Miller, L. W. (2017) Time-Gated Detection of Cystathionine gamma-Lyase Activity and Inhibition with a Selective, Luminogenic Hydrogen Sulfide Sensor, Chemistry 23, 752-756.

Our published contributions to anti-infective drug discovery derive from two long-term collaborations with lijun Rong on inhibition of viral entry and with David Williams on Schistosomiasis, disease caused by infection with freshwater parasitic worms in tropical and subtropical countries. Inhibition of viral entry can be effective in vitro and in mouse models, but as we have been learning with SARS-CoV-2: 1) drugs such as remdesivir that seem effective in vitro have very little clinical efficacy; and, 2) the individual response to infection varies widely and is not simply related to viral load. In March, we initiated a project to discover small molecules that inhibit the interaction of CoV-2 viral proteases with human target proteins that disrupt the immune system.

1. Cooper, L., Schafer, A., Li, Y., Cheng, H., Medegan Fagla, B., Shen, Z., Nowar, R., Dye, K., Anantpadma, M., Davey, R. A., Thatcher, G. R., Rong, L., and Xiong, R. (2020) Screening and Reverse-Engineering of Estrogen Receptor Ligands as Potent Pan-Filovirus Inhibitors, J Med Chem.
2. Gaisina, I. N., Peet, N. P., Wong, L., Schafer, A. M., Cheng, H., Anantpadma, M., Davey, R. A., Thatcher, G. R. J., and Rong, L. (2020) Discovery and Structural Optimization of 4-(Aminomethyl)benzamides as Potent Entry Inhibitors of Ebola and Marburg Virus Infections, J Med Chem 63, 7211-7225.
3. Gaisina, I. N., Peet, N. P., Cheng, H., Li, P., Du, R., Cui, Q., Furlong, K., Manicassamy, B., Caffrey, M., Thatcher, G. R. J., and Rong, L. (2020) Optimization of 4-Aminopiperidines as Inhibitors of Influenza A Viral Entry That Are Synergistic with Oseltamivir, J Med Chem 63, 3120-3130.
4. Lyu, H., Petukhov, P. A., Banta, P. R., Jadhav, A., Lea, W. A., Cheng, Q., Arner, E. S. J., Simeonov, A., Thatcher, G. R. J., Angelucci, F., and Williams, D. L. (2020) Characterization of Lead Compounds Targeting the Selenoprotein Thioredoxin Glutathione Reductase for Treatment of Schistosomiasis, ACS Infect Dis 6, 393-405.
5. Silvestri, I., Lyu, H., Fata, F., Boumis, G., Miele, A. E., Ardini, M., Ippoliti, R., Bellelli, A., Jadhav, A., Lea, W. A., Simeonov, A., Cheng, Q., Arner, E. S. J., Thatcher, G. R. J., Petukhov, P. A., Williams, D. L., and Angelucci, F. (2018) Fragment-Based Discovery of a Regulatory Site in Thioredoxin Glutathione Reductase Acting as "Doorstop" for NADPH Entry, ACS Chem Biol 13, 2190-2202.
6. Ziniel, P. D., Karumudi, B., Barnard, A. H., Fisher, E. M., Thatcher, G. R. J., Podust, L. M., and Williams, D. L. (2015) The Schistosoma mansoni Cytochrome P450 (CYP3050A1) Is Essential for Worm Survival and Egg Development, PLoS Negl Trop Dis 9, e0004279.