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.
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.
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.
Benedikt Grau, Ph.D.
Education: Ph.D., Chair of organic Chemistry II, Friedrich-Alexander-University Erlangen-Nuernberg, Germany.
Scientific interests: Dr. Grau is interested in the development of novel synthetic methodologies and their utilization in the synthesis of natural product inspired small molecule scaffolds. With his colleagues in the biological department, he aims to identify correlations between bioactive molecule motifs and their bioactivity. His research expertise includes organic and medical chemistry, organocatalysis, multi-step synthesis, hybridisation, and drug discovery.
Dr. Grau completed his PhD under the supervision of Professor S. B. Tsogoeva in October of 2021 at Friedrich-Alexander University in Erlangen, Germany. His research mainly focused on the development of novel base or organocatalyzed one-pot procedures and domino-reactions towards novel terphenyl core structures. Triarylbenzenes (TAB), which bore three different functional groups and enabled the development of a multi-step synthesis route towards Hexaarylbenzene (HAB) with 6 different rings. This work identified novel scaffolds and hybrid-molecules exhibiting bioactivity in the treatment of diseases e.g., malaria, cancer, the coronavirus (COVID-19) and the human cytomegalovirus (HCMV).
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.
Sreenu Jennepalli, Ph.D.
Education: Ph.D., Organic synthesis, Medicinal Chemistry, University of Wollongong, Wollongong, Australia.
Scientific interests: Dr. Jennepalli is a Research Associate at the OHSU Knight Cancer Institute’s Center for Experimental Therapeutics (CET). He works on new therapeutic targets with applications in Cancer and Cardiovascular research. His research expertise includes Organic and Medicinal chemistry, peptide synthesis, carbohydrate and nucleoside chemistry and drug discovery.
Dr. Jennepalli worked as a drug discovery Scientist in leading drug discovery companies such as Dr Reddy’s laboratories and Hetero Drugs Ltd, in India. He mainly worked on anti-cancer, cardiovascular and anti-viral drug development. He was a significant contributor in one of the PHASE II clinical trial Cardiovascular drugs from Dr. Reddy’s Laboratories. He then pursued his Ph.D. in Chemistry from the University of Wollongong, Australia, where his research focused on the synthesis of C60 Fullerenyl amino acids and water-soluble peptides, and peptidomimetics for medicinal chemistry applications. During postdoctoral work at the UOW and University of New South Wales, he worked on the synthesis and development of cationic peptidomimetic amphiphiles as anti-bacterial drug candidates. He also has experience in organometallic chemistry and polymer chemistry. With over 15 years of organic synthesis and drug discovery experience, at the CET, Sreenu will design and synthesize small molecules for translational research in the fields of cancer and cardiovascular diseases.
Wendy Li, M.S.
Research Assistant 2
Education: M.S., Toxicology, University of Kentucky.
Scientific interests: Wendy is a research assistant, interested in biochemistry and biology in oncology, and the transformations under treatments. After obtaining her Master’s degree of Toxicology from University of Kentucky, Wendy studied the effects of heavy metals as carcinogen in skin, lung and colon cancer. She joined OHSU in 2017 to work with the Bergan lab, on novel compounds for experimental prostate cancer treatments. Wendy joined Malhotra group in 2021. She is working with the team on discovery and development of small molecules for experimental therapeutics.
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.
Kirsten Stefan, Ph.D.
Scientific Interests: Dr. Stefan is interested in drug discovery for sarcomas in a bench to bedside approach to help bring novel therapies to patients. Her Ph.D. work was focused on the effects of omega-3 polyunsaturated fatty acids on T cell function as it relates to inflammation and autoimmunity. Her post-doctoral training in the Department of Immunology at Baylor College of Medicine explored detailed mechanisms of autoimmunity, with particular focus on T cell and B cell involvement. Most recently, Dr. Stefan served as research scientist at M.D. Anderson Cancer Center discovering means of immunotherapy for osteosarcoma including investigation of chimeric antigen receptor (CAR) T cell therapies. Prior to her focus in osteosarcoma, she worked at M.D. Anderson to help bring CD19-CAR T cells into clinical trial.
Julia Stokes, B.S.
Education: B.S., Cellular, Molecular, & Developmental Biology, University of Washington Seattle. Graduate Student in Program for Biomedical Science at OHSU
Scientific interests: Julia Stokes is a graduate student in the Program for Biomedical Science. After obtaining her B.S. (Cellular, Molecular, Developmental Biology) at University of Washington, she worked at Seattle Children’s Research Institute under the guidance of Dr. Simon Johnson, studying underlying mechanisms of Leigh’s Syndrome progression through mTOR signaling pathways using FDA approved pharmacological treatments (Rapamycin, Pexidartinib, etc..). Due to her research experience, she developed a strong interest in translational medicine and developing small molecule targeted therapies for various complex genetic dysfunctions. Since joining Malhotra’s Lab, Julia has started her thesis work studying small molecules that could potentially target Melanocortin-4 Receptor (MC4R) for therapeutic purposes. After graduate school, her goal is to pursue her postdoc and eventually open her own lab with a focus in translational medicine for genetic diseases caused by immune or mitochondrial disorders.
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.
Expected B.S. in Biology and Studio Art, Davidson College
2021 Summer Intern
Scientific interests: Pearce is an undergraduate intern in the Malhotra lab. His work focuses on assay development for G-couple protein receptors (GPCRs). GPCRs are a wide and diverse set of eukaryotic receptors. Nearly 1/3 of all prescribed medication uses GPCRs, but many have unknown agonists. This summer's research has been developing assay techniques to test GPR39s ability to bind novel agonists. If stimulated, GPR39 has numerous therapeutic benefits ranging from recovery after hemorrhagic stroke to insulin secretion in pre-diabetic patients. With no native ligand, however, this assay development is crucial in order to find novel agonists with drug-like potential. He has developed procedures for calcium mobilization and B-arrestin assays in our lab that can be applied in order to rank new agonists for drug-like potential.
Maria (Tori) Lopez
Current undergraduate student, George Fox University
2021 Summer Intern
Scientific interests: This summer Tori is working in Malhotra lab specifically studying the different cellular responses of a combination and monotherapy of prostate cancer (CaP) treatment. The research specifically focuses on the investigation of a novel therapeutic strategy for inhibiting advanced CaP. CaP is a disease that kills many men in the United States. Current therapies for treating advanced CaP are poorly effective, typically only extending patient’s lives by a few months. Recognizing an obvious need for a more efficient therapy that will inhibit cancer cell growth, our lab synthesized a new drug targeting a key driver of CaP. To do so Tori focused on the TMPRSS2-ERG gene fusion, the most prevalent genomic alteration observed in CaP patients. This fusion causes an upregulation of ERG protein expression, which results in enhanced cancer growth and causes cancer to spread to distant sites in the body, a process known as metastasis. Specifically, Tori’s project works on characterizing the therapeutic efficacy of an ERG inhibitor that our lab synthesized when used as a standalone agent and in combination with chemotherapy, upon a variety of prostate cancer cell lines.
Ryan Gordon, Ph.D.