Laurie G. Hudson, Ph.D. – 2025 Rainforest Innovation Fellow

An Innovators Journey

I was always curious about the natural world. Growing up in semi-rural Washington State provided many opportunities to observe and interact with nature, but I never imagined these inclinations might become a career. I didn’t expect to attend college—my upbringing was centered on traditional roles, the value of hard work and practical outcomes. There were two major inflection points that changed my future. My high school chemistry teacher offered quiet support and fostered my science interests while my French teacher insisted I take the SAT. My appreciation for Mr. Clow’s and Mrs. Franklin’s persistent nudges shows up in my commitment to mentorship. I know that acting on belief in someone can be a powerful force. The other inflection point was a scholarship opportunity through my father’s employer, the Burlington Northern Railroad. The interviewers challenged me to have larger aspirations, and more importantly, granted me the scholarship that made attendance at the University of Washington possible.

I entered my freshman year at the University of Washington as a first-generation college student woefully ignorant of how to navigate a school that was larger than my home town. I continued to find my intellectual home in science and majored in Zoology. Science was my path, but the destination was unclear until spring quarter of my junior year. Dr. Lynn Riddiford led a course teaching students specific research techniques that they would then apply to their own independent research question. This was my introduction to the wonder of research, and I realized that the process of inquiry was the way I wanted to keep learning. This revelation was reinforced by my time with Dr. Lawrence Loeb’s laboratory studying the fidelity of DNA replication. I was too naïve to understand I had entered the realm of a true luminary, but I was thrilled to be part of, and contribute to, the pervasive excitement in his lab. This experience further fueled my love for research and desire to pursue a Ph.D.

I was accepted into the inaugural class of the Toxicology Program at Harvard Medical School. I studied the effects of TCDD, a highly toxic component of the defoliant Agent Orange, on human skin cells with Drs. William F. Greenlee and William A. Toscano. We established that human cells had specific receptors for TCDD and this toxin disrupted normal skin biology by interfering with signaling pathways such as the EGF receptor. A recent discovery that the avian viral oncogene v-erbB was related to the EGF receptor and human cancer prompted my decision to step away from toxicology for my post-doctoral work. I joined Dr. Gordon Gill’s group at the University of California, San Diego based on his expertise with receptor tyrosine kinases. The research topic was highly competitive and unfortunately, my first two years of work were “scooped”—published by another laboratory. In the midst of this disappointment a friend from Seattle contacted me about a toxicology consultant position and to my surprise, I wasn’t tempted. My love for research ignited at the University of Washington didn’t waver and I shifted gears toward researching transcriptional regulation of the EGF receptor supported by an NIH F32 postdoctoral fellowship. My graduate mentor Bill Toscano was fond of saying, “there’s always plenty of science to do,” and that truth has been helpful for coping with the inevitable obstacles inherent in research.

My work as a faculty member at Northwestern University Medical School and then at the University of New Mexico (UNM) College of Pharmacy merged my interests in basic cellular mechanisms of cancer and toxicology. The EGF receptor remained a focal point because of burgeoning evidence for the role of the ErbB family of receptors in cancer progression and as therapeutic targets. We investigated how the EGF receptor regulated cell plasticity in models of wound repair, skin cancer and ovarian cancer. Over-expression and mutational activation of the EGF receptor promoted dramatic changes in cell behavior. This was true for normal skin tissue during wound repair where EGF receptor levels are transiently increased and in the tumor models of persistent EGF receptor activation. The EGF receptor is also sensitive to a range of environmental stimuli so we conducted studies of EGF receptor activation by ultraviolet radiation and arsenic. These are both prevalent environmental exposures in New Mexico and it seemed like an appropriate toxicology question for my adopted state.

Ultimately, these parallel arms of research progressed in new directions based on evolving evidence and collaborative opportunities. There was an intriguing finding that co-exposure to ultraviolet radiation and arsenic synergistically increased tumors in mouse models of skin cancer. My colleague Dr. Ke Jian (Jim) Liu and I found that arsenic blocked the repair of DNA damage caused by ultraviolet radiation leading to persistent DNA damage and increased mutations. Further work showed that arsenic selectively disrupted the function of certain zinc-dependent DNA repair proteins and supplemental zinc protected cells and mice from this arsenic-mediated toxicity. Because zinc-dependent proteins are essential for broad aspects of human health, the protective effects of zinc held potential to benefit people chronically exposed to toxic metals. This logical outgrowth from the mechanistic insights became a project in the UNM METALS Superfund Center with Dr. Debra MacKenzie, including an ongoing clinical trial to test whether zinc supplementation mitigates toxicity in people exposed to legacy uranium mine waste on the Navajo Nation.

Sometimes new evidence opens doors and other times not. Clinical interest in EGF receptor-targeted therapeutics for ovarian cancer waned when early clinical trials failed to show patient survival benefits. Faced with that closed door, my colleague Dr. Angela Wandinger-Ness and I embarked on studies for an alternate approach to block tumorigenic pathways in ovarian cancer based on small GTPases such as Rac1. Rac1 regulates cell growth and survival, metastatic behaviors, angiogenesis and other key features of cancer. Lead inhibitors of Rac1 and related GTPases were identified through high throughput screening conducted by Dr. Larry Sklar and colleagues. Computational approaches by Drs. Tudor I. Oprea and Oleg Ursu predicted inhibitory potential for the R-enantiomer of the FDA-approved drug ketorolac and ketorolac had potential for human testing. This in turn made a pilot clinical trial led by physician scientists Drs. Carolyn Muller, Teresa Rutledge and Sarah Adams feasible and paved the way for our additional studies testing the potential benefits of R-ketorolac as a therapeutic for ovarian cancer. It has been my great privilege to have two projects progress from basic bench research to human studies in the company of such wonderful colleagues.

The comedian Amy Poehler has said, “find a group of people who challenge and inspire you, spend a lot of time with them, and it will change your life forever.” I find these words to be true—my life has been changed for the better by my mentors, my colleagues, those I have had the privilege to mentor, and the vast support network and inspiration at UNM. The current and past members of my laboratory have my special affection and respect for their perseverance through the small and large frustrations of conducting research, grace in juggling work and home responsibilities (including the twelve babies born to the group), and all the beautiful individual selves they brought into my life. My wonderful husband Gregg LaPore has been at my side since our days in Seattle and provides steadfast love and support. I am also grateful for the efforts of UNM Rainforest Innovations to shepherd the outcomes of collective scientific effort toward real-world application and the various funding entities supporting the research.