My research interests focus on the design and discovery of synthetic and natural product inspired small molecules, which can provide insight into biological mechanisms and disease targets. My laboratory employs the tools of synthetic medicinal chemistry, molecular modeling and chemical biology for translational research in drug discovery, development, imaging and radiation. The key aims of my research are (i) to design probe molecules that can be used to characterize the functions of particular proteins or drive specific cellular phenotypes, (ii) discover compounds that could be turned into drugs for human diseases and, (iii) educate the next generation of drug hunters.
Mallesh Pandrala, Ph.D.
Assistant Staff Scientist
Education: Ph.D., Chemistry, University of New South Wales (UNSW), Canberra, Australia.
Scientific interests: Dr. Pandrala is an assistant staff scientist at the OHSU Knight Cancer Institute’s Center for Experimental Therapeutics (CET). He works with colleagues in chemical biology and biology to drive the discovery of new therapeutics with applications in cancer and microbial research. His research expertise includes organic and inorganic chemistry, peptide synthesis, medicinal chemistry, drug discovery, and pharmacokinetic studies.
Dr. Pandrala worked as a process chemist and drug discovery chemist in leading drug discovery companies such as Dr Reddy’s laboratories and Jubilant Biosys in India. He then pursued his Ph.D. in Chemistry from the University of New South Wales (UNSW) Canberra, Australia, where his research focused on therapeutic properties of mono- and di- nuclear Iridium(III) complexes. During postdoctoral work at the University of Puerto Rico (UPR-Rio Piedras), he developed synthetic strategies to conjugate small molecules to bioactive peptides to improve selective drug delivery to cancer cells. As a postdoctoral researcher and research scientist in the Department of Radiation Oncology, Stanford University, he developed small molecule kinase inhibitors of the BCR-ABL1 oncogene, small molecules that can be utilized in preventing or reversing T cell exhaustion. He developed strategies to synthesize prodrugs for approved drugs to improve their pharmacokinetic properties. Furthermore, he developed pharmacokinetic assays using LC-MS for various drug molecules. With over 12 years of organic and inorganic synthesis and drug discovery experience, at CET, Mallesh will design and synthesize small molecules for translational research in the fields of cancer and microbiology. In addition, he is interested in developing strategies to study pharmacokinetics of new drug molecules.
Marie Foss, Ph.D.
Senior Research Associate
Education: Ph.D., Biochemistry, University of Wisconsin-Madison; B.S., Chemistry, Biochemistry, University of Minnesota-Duluth.
Scientific interests: Dr. Marie Foss is interested in research at the interface of chemistry and biology, especially the discovery of chemical biological tools to study biological systems and small molecule drug development. She obtained her B.S. (chemistry, biochemistry) from the University of Minnesota-Duluth with training in synthetic chemistry from Prof. Steven Berry. Her graduate education at the University of Wisconsin-Madison in biochemistry involved the study of bacterial physiology under the direction of Prof. Douglas Weibel. Dr. Foss received postdoctoral training in the tuberculosis host-pathogen interface at OHSU under the guidance of Prof. Georgiana Purdy. Most recently, Dr. Foss served as senior research scientist at Neuralexo, INC to develop agonists of the innate immune system. Dr. Foss is encouraged by the potential that engagement of the innate immune system has for the treatment of cancer and looks forward to the development of therapeutics based on this strategy.
Dhanir Tailor, Ph.D.
Postdoctoral Research Fellow
Education: Ph.D., Cancer Biology, Central University of Gujarat, India.
Scientific interests: Dhanir Tailor earned his Ph.D. in Cancer Biology from Central University of Gujarat, India in 2016. A primary focus of his thesis work was directed towards understanding the effect of physiological concentrations of butyric acid on human colorectal cancer (CRC) cell death and mitochondrial dynamics. Short-chain fatty acids including butyric acid, propionic acid, and acetic acid are present in millimolar concentrations in gastrointestinal tract, which are mainly synthesized by our gut microbiome. These short-chain fatty acid molecules have been shown to affect biological events such as cell cycle progression, differentiation and programmed cell death. Initially, he screened various short chain fatty acid (SCFA) for their cancer preventive efficacies, among which, he found Butyric acid (BA) to be a potential candidate with chemo-preventive role. His studies showed that BA decreased the overall population/mass of active mitochondria in CRC cells, which could be an indicator of mitochondrial fusion. BA mediated effect is brought about by its reduction of Dynamin related protein 1 (DRP1) protein, which is a key regulator of mitochondrial fission and fusion processes. These findings suggest that DRP1 could be a potential molecular target to induce mitochondrial fusion and inhibition of mitochondrial fission mediated by BA treatment in CRC cells. Furthermore, overexpression of DRP1 in CRC cells enhanced the rate of cell proliferation and migration. This study is the first molecular and cell culture based evidence which sheds light on the ‘Role of DRP1 in CRC cancer growth, survival and progression’.
After three years of research at Stanford University, Dhanir joined the Department of Cell, Developmental & Cancer Biology at Oregon Health & Science University in August 2020 as Postdoctoral Research Fellow and is currently working to develop radio-sensitizers, and small molecule probes to study treatment resistance.
Arpit Dheeraj, Ph.D.
Postdoctoral Research Fellow
Education: Ph.D., Cancer Biology, Jawaharlal Nehru University, India.
Scientific Interests: Arpit Dheeraj completed his Ph.D. in Cancer Biology in 2019 from Jawaharlal Nehru University, India under the guidance of Prof. Rana P. Singh. The primary focus of his dissertation work was to understand the role of IGFBP-3 (Insulin-like Growth Factor Binding Protein-3), an essential component of the IGF system, on prostate cancer progression. Objectives of the study were to identify the effects of IGFBP-3 on tumor angiogenesis and metastasis under normoxia and hypoxic conditions. His studies showed that IGFBP-3 inhibited the overall growth of prostate cancer cells, IGFBP-3 overexpression inhibited angiogenesis, and reduced endothelial cell growth and migration. IGFBP-3 modulated the expression of different mitogenic and pro-survival signaling mediators which resulted in the altered biological function of cancer cells. IGFBP-3 overexpression inhibited migration under normoxic conditions; however, within the hypoxic environment, IGFBP-3 overexpression increased cell migration. Overall, these findings show that IGFBP-3 targets different steps of prostate cancer growth and progression and it could be a potential therapeutic target.
Arpit is studying the mechanism of treatment resistance in Head & Neck, and Triple negative breast cancer using chemical probes developed in Malhotra lab.
Senior Research Assistant
Education: B.Sc., Cell and Molecular Biology, University of Michigan-Ann Arbor.
Scientific interests: Alexander Honkala is a scientist and entrepreneur whose interests range from immunology to mathematical oncology with a passion for the complex systems of disease and translation of new drugs to the clinic. He earned his B.Sc. in Cell and Molecular Biology from the University of Michigan – Ann Arbor in 2008 and has gone on to found nonprofits and biotech start-ups. As a founder, director, consultant, and CEO, Alexander has played a wide variety of roles in the development of new projects across a wide range of interests. Alexander innately looks for the edges of any system he works with, trying to find the path from its well-known key principles to its various bleeding edges to imagine what may lie just around the corner. Oriented towards the next step, whatever it may be, Alexander is excited to keep working at the forefront of oncology, immunology, and drug development to tackle complex conditions with a balance of new drugs and incisive development strategy. When he’s not working on one of several projects, he can be found out on the hiking trails soaking in the forest, in the kitchen making a mess, or in the studio making noise.