Our Research
Overview
Greg Thatcher joined the University of Arizona in 2020 from the University of Illinois College of Pharmacy. 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. Most importantly, in 2013, he founded a campus-wide and disease-agnostic drug discovery center at UIC, focused on small molecule therapeutics, which continues to play an active role in academic drug discovery across Chicagoland bioecosystem. Dr Thatcher created his first start-up biotech company in 1997, which successfully took an Alzheimer’s drug into human clinical trials. The Thatcher lab’s research has been continuously funded by the NIH since 2003, supported by NCI, NIA, NHLBI, and NIAID, resulting in over 170 publications and dozens of issued patents. Two new chemical entities that were licensed and successfully completed Phase 1 clinical trials for metastatic breast cancer in 2019, Rintodestrant and TTC-352, are proceeding in the clinic. For publications on therapeutics invented by Thatcher and his team, which have been trialed in human subjects.
In his career, he has graduated over 50 students with PhD’s, a dozen with Masters degrees, and mentored 40 undergraduate researchers; the majority of the undergrads 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.
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 can expect a multidisciplinary education. For example, students who graduate having focused their research on synthetic medicinal chemistry will have competency in another area, such as drug metabolism and pharmacokinetics. Students who focus their research on cell-based models or animal models will be experts in bioassay design and will have competency in drug design and discovery. Access to modern techniques in cell engineering, mass spectrometry, and proteomics provides students with highly employable skills; however, students are expected to have fun during their progress to graduation as doctors of philosophy.
Aging
Compared to 1990, life expectancy has increased from 73 to almost 80 for women and from 67 to 73 years old for men in high income countries; whereas globally life expectancy is currently 76 for women and 71 for men. Healthy life expectancy globally is 65 and 62 for women and men, respectively. In one analysis, the number of years gained in the USA is split equally between years in poor health and years in good health. Aging is the greatest risk factor for Alzheimer’s disease and related dementia. In women, the number of years lost to ill-health caused by Alzheimer’s disease ranked #33 in 1990, #22 in 2007, and #15 in 2017. Although women live longer than men, half of that increased lifespan is spent in poor health. Human aging is extremely difficult to model in the lab, even without adding the complexity of human dementia and remembering that Alzheimer’s disease can only be definitely diagnosed post-mortem.
Cancer
Cancer has been with mankind throughout recorded history. Cancer describes numerous human maladies characterized by reprogramming of our own human cells causing unregulated growth, either in the blood, or in tissues leading to solid tumors. In general, metastatic disease describes the progression and dispersal of the primary cancer or tumor cells to other organs. In the last century, natural products provided the backbone of cancer chemotherapy. These natural products were developed by organisms to kill other competitor organisms and this cytotoxicity was harnessed to kill cancer cells; however, cytotoxic chemotherapy has severe and unpleasant side effects. Targeted therapies that are generally not cytotoxic, but target specific vulnerabilities that are amplified in cancer cells, have had a significant impact in treating cancer. More recently, immuno-oncology has also had major impact. Nevertheless, resistance to therapy often leads to metastatic disease, needing new therapeutics.
Anti-Infectives
The COVID-19 pandemic has focused the thoughts of society on pathogens. These range from bacteria, fungi, and worms that are very much alive to viruses, the vitality of which is problematic. As in cancer chemotherapy, natural products, designed to kill competing organisms, have supplied our arsenal of anti-infective therapeutics; and as in cancer, resistance is an issue. Bacteria are studied as components of the microbiome, increasingly appreciated to contribute to human health and disease. Equally, the worm, C. elegans is allowing the study of aging and target identification for drugs directed at human diseases. Our disease-agnostic approach to drug discovery permits pivoting from using small molecules in breast cancer to re-engineering these molecules for Ebola antiviral therapy.