As a translational scientist, Aneel Paulus, M.D., conducts scientific investigations that seek to address the clinical challenges of patients with hematologic cancers. Because there is an incomplete molecular understanding of these challenges, Dr. Paulus centers his research on the biomolecular and immunologic mechanisms associated with drug resistance in B-cell cancers.
Dr. Paulus' team utilizes advanced computational, genomic and immunology-based techniques to study the effects of targeted-therapies on tumor-cell signaling pathways and how this influences their interaction with the innate and adaptive immune system. Based on this work, Dr. Paulus' long-term goal is to develop molecularly individualized therapeutic strategies and diagnostic tests for patients with incurable malignancies such as multiple myeloma, Waldenstrom macroglobulinemia and chronic lymphocytic leukemia.
To accomplish this goal, Dr. Paulus has active academic collaborations with clinical and basic science colleagues at Cornell University, Roswell Park Cancer Institute, Sanford-Burnham Prebys Medical Discovery Institute and Karolinska Institutet in Sweden.
- Discovery of novel therapeutic targets. Using molecular profiling and analytic techniques, Dr. Paulus and his team have discovered new proteins and receptors that play a role in resistance to proteasome inhibitors and BTK-inhibitors. Dr. Paulus is actively studying the function of these new targets and how they can be selectively disrupted in tumor cells. In collaboration with Thomas Caulfield, Ph.D., Head of Drug Discovery at Mayo Clinic's campus in Florida, Dr. Paulus is developing new small molecule inhibitors that are targeted specifically at these proteins, for therapeutic purposes.
- Drug development from natural sources. Various herbs, plants and trees are known to possess medicinal qualities. Dr. Paulus and his team have identified and isolated the key phytochemical component of a medicinal herb with potent anti-tumor properties. Using this naturally occurring chemical as a starting point, he and his team have synthesized a diverse set of structural analogs (drug-like chemicals), each designed to target specific proteins relevant in B-cell malignancies.
- Development of companion diagnostic tests. An accurate and precise screening test can identify patients who are likely to benefit from a particular treatment before its use. Based on the expression pattern of specific enzymes, Dr. Paulus is working on a laboratory test that would identify whether a multiple myeloma patient should receive bortezomib-based therapy and predict, at a molecular level, whether a patient who is currently on bortezomib will eventually acquire resistance to its effects. This test would allow for optimal use of bortezomib-based treatments in the appropriate patient populations, preventing its unnecessary use and possible side effects.
- Integration of clinical, genomic and computational technologies for individualized medical care. Recognizing that the value of existing molecular and genomic profiling assays can be significantly augmented with machine-learning algorithms and massively parallel computing, Dr. Paulus and collaborators are preclinically testing advanced computational technologies that are capable of predicting biological responses to a variety of treatments in individual patients. This novel method is performed in a high-throughput and cost-effective manner and will soon enter clinical stages of validation.
Significance to patient care
Drug resistance remains an enormous challenge for the vast majority of cancer patients as well as the oncologists who treat them. Dr. Paulus' research in the arena of drug pharmacology, biochemical activity and incorporation of advanced biotechnologies in the clinical workflow is positioned to enhance the ability of clinical decision-making at the point of care. His goals of deciphering the molecular determinants of drug activity are leading to the development of new therapies and tests, and may ultimately improve the overall survival of patients with B-cell malignancies.
- Principal investigator, Gerald A. and Margaret A. Wellik Development Award in Lymphoma Research, 2016, 2018
- Co-investigator and site principal investigator, Mayo Clinic Multiple Myeloma Biospecimens Core, 2016-present
- Co-investigator, Mayo Clinic Multiple Myeloma SPORE Career Enhancement Award, 2015-2017
- Principal investigator, Henry J. Predolin Foundation Career Development Award, 2015-2016
- Principal investigator, University of Iowa/Mayo Clinic Lymphoma SPORE Developmental Research Award, 2014-2016
- Recipient, Mayo Clinic Cancer Focused Research Team Awards, 2015, 2016
- Recipient, American Society of Hematology Merit Award, 2014, 2015