Faculty

Research Summary

Primary areas of research interest include studying cell behavioral responses to natural, synthetic, and semisynthetic compound candidates for cancer chemotherapy, including investigating the role of the physical microenvironment in mechanotransduction and chemotherapeutic action using three-dimensional in vitro culture systems. Recent projects are focused on exploring the interplay between microenvironmental compliance, the expression of certain C2H2 zinc finger transcriptional regulators, and their modulation by mevalonate pathway inhibitors. Collaborative studies have included using two-photon fluorescence polarization anisotropy of NADH to study cell metabolic responses to novel perturbants of glycolysis and oxidative phosphorylation (Drs. A. Heikal and V. Mereddy, Univ. of MN Duluth), and the actions of natural and semi-synthetic mitochondrial-targeting compounds on various tumor cell lines (Dr. P. Krasutsky, NRRI, and the MitoXT research group of the CNC led by Dr. P. Oliveira, Univ. Coimbra, Portugal).

Teaching Summary

Cell Biology

Mentoring/Advising: undergraduate students, graduate students, and post doctoral researchers.

Teaching Summary

I am an anatomist, functional morphologist, and paleoanthropologist interested in primate locomotion. Specifically, I focus on hindlimb form-function relationships in extant and fossil primates, including humans and hominins, in order to better understand movement in living organisms as well as how fossil taxa interacted with their environment. I investigate how both external bony morphology and internal trabecular bone structure relate to movement. Since 2019 I have been affiliated with the Koobi Fora Research and Training Program (KFRTP) where I work with an international, interdisciplinary team of researchers in Kenya in collaboration with the National Museums of Kenya to find additional evidence of our hominin ancestors as well as reconstruct the environment in which they lived and the resources they had available to them.

Bio

Sarah E. Lacher, Ph.D. is an Assistant Professor in the Department of Biomedical Sciences at the University of Minnesota Medical School and a member of the Cellular Mechanisms of Cancer Program at the University of Minnesota Masonic Cancer Center. Dr. Lacher’s research focuses on characterizing cell-type specific patterns of gene regulation following exposure to various inducers of oxidative stress. In addition to her commitment to research, Dr. Lacher is a dedicated educator. She is leading the Pharmacology Thread in the new bi-campus curriculum build, and in 2022 Dr. Lacher was Awarded the Basic Science Teacher of the Year by the Medical Students. Dr. Lacher is also involved in STEM outreach activities through the University of Minnesota's Innovators of the Future, Bois Forte Community Based Science and QueerScience Programs. Dr. Lacher received her BS in Biology with an emphasis in Secondary Education from University of Northern Colorado (2006). She then taught Secondary Science in Colorado before attending graduate school. Dr. Lacher earned a PhD in Toxicology from the University of Montana (2013), and was a Postdoctoral Associate at the University of Minnesota Medical School (2013–2018). Dr. Lacher is a member of the Society of Toxicology and is a Founding Executive Board Member of the newly established Special Interest Group, Out Toxicologists and Allies (OTA). She is also a member of Women in Toxicology (WIT), Hispanic Organization of Toxicologists (HOT) and the Northland Regional Chapter of the Society of Toxicology.

Publications

• Sarah E Lacher, Cara Skon-Hegg, Brian L. Ruis, Jennifer Krznarich, Matthew Slattery. An antioxidant response element regulates the HIF1α axis in breast cancer cells. Free Radic Biol Med. 2023 Aug 1; 204:243-251
• Sade Spencer, Catherine Burrows, Sarah E. Lacher, Kait Macheledt, Jerica M. Berge , Rahel G. Ghebre, Framework for advancing equity in academic medicine and science: Perspectives from early career female faculty during the COVID-19 pandemic: Preventive Medicine Reports. 24;  101576, 2021
• Daniel C.Levings*, Sarah E.Lacher*, Juan Palacios-Moreno, Matthew Slattery, Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape, (*) - indicates co-first author): Free Radical Biology and Medicine, 171: Pages 319-331, 2021
• Daniel C. Levings, Kirsten E. Shaw, Sarah E. Lacher, Genomic Resources for Dissecting the Role of Non-Protein Coding Variation in Gene Environment Interactions: Toxicology, 441, 2020 
• Sarah E. Lacher, Daniel C. Levings, Samuel Freeman, Matthew Slattery, Identification of a Functional Antioxidant Response Element at the HIF1A Locus: Redox Biology, 19: 401-411, 2018
• Sarah E. Lacher, Xuting Wang, Douglas A Bell, Roger Pique-Regi, Francesca Luca, Matthew Slattery, A Hypermorphic Stress-responsive cis-regulatory Element is Associated with Increased MS4A6A Expression and Alzheimer’s disease; Redox Biology, 14: 686-693, 2018
• Sarah E. Lacher, Matthew Slattery. Gene Regulatory Effects of Disease Associated Variation in the NRF2 Network. Current Opinion in Toxicology, 1: 71-79, 2016
• Xuting Wang, Michelle R. Campbell, Sarah E. Lacher, Hye-Youn Cho, Ma Wan, Christopher Crowl, Brian N. Chorley, Gareth L. Bond, Steve R. Kleeberger, Matthew Slattery, Douglas Bell. A Strong Nrf2 Binding Allele in the MAPT Gene Enhances Expression and is Protective in Parkinsonian Disorders. Cell Reports; 15: 4, 830-842, 2016
• Sarah E. Lacher, Joslynn S. Lee, Xuting Wang, Michelle Campbell, Douglas Bell, Matthew Slattery. Beyond Antioxidant Genes in the Ancient Nrf2 Regulatory Network. Free Radical Biology and Medicine; Special Issue: Nrf2 Regulated Redox Signaling and Metabolism in Physiology and Medicine; 88: B, 452-465, 2015.
• Sarah E. Lacher, Kasse Skagen, Joachim Veit, Rachel Dalton, Erica L. Woodahl. P-glycoprotein Transport of Neurotoxic Pesticides. Journal of Pharmacology and Experimental Therapeutics; 355: 99-107, 2015
• Sarah E. Lacher, Julia N. Gremaud, Kasse Skagen, Emily Steed, Rachel Dalton, Kent D. Sugden, Fernando Cardozo-Pelaez, Catherine M.T. Sherwin, Erica L. Woodahl. Absence of P-glycoprotein Transport in the Pharmacokinetics and Toxicity of Herbicide Paraquat. Journal of Pharmacology and Experimental Therapeutics; 348(2): 336-345, 2014.
• Sarah E. Lacher, Corbin Johnson, Forrest Jessop, Andrij Holian, Christopher T. Migliaccio. Murine Pulmonary Inflammation Model: A comparative Study of Anesthesia and Instillation Methods. Inhalation Toxicology; 22(1): 77–8, 2010

Other Publications

Research Summary

Reactive oxygen species (ROS) are the byproducts of oxygen metabolism and are necessary molecules for cell signaling, homeostasis, and development. However, the balance between cellular oxygen and damaging ROS levels needs to be finely tuned; disruption in redox homeostasis often leads to cytotoxicity and can ultimately result in irregularities in development and pathology. Fortunately, cells have evolved mechanisms that allow them to directly combat disruptions in oxygen homeostasis and keep ROS levels tightly balanced to mitigate such effects. Cells rely heavily on the activity of transcription factors (TFs) in order to execute global gene expression changes. When it comes to oxygen sensing, one of the most important TFs is NRF2 (Nuclear factor (erythroid-derived 2)-like 2). Recently, we have come to better understand the ancient mechanism of global gene regulation by NRF2 in response to oxidative stress; in addition, we have also recently identified and functionally validated a number of novel NRF2 target genes. However, our current understanding of NRF2's capability at selectively controlling antioxidant genes needs to be greatly extended in order to understand its global control of a multitude of mechanisms central to the cell's response to oxidative stress.

Teaching Summary

Problem Based Learning Facilitator: Cardiovascular, Respiratory, Renal, Acid-Base-I & II, Immunology, Hematology, and Oncology, Skin and Musculoskeletal, and Neurological Medicine Courses.

Lecturer: Foundations of Medicine, Social and Behavioral Medicine, Hormonal and Reproductive Medicine, Current Topics in Functional Genomics, and Introduction to Pharmacology. 

Mentoring/Advising: Undergraduates, Graduate students, and Postdoctoral Associates

Teaching Awards
Basic Science Teacher of the Year- 2021/2022

Research Summary

I have a long-standing interest in the functional recovery of sensory and motor functions after brain injury, such as stroke. I have been exploring technologies that can improve the functional recovery in stroke patients. Specifically, how is the somatosensory input processed in the primary somatosensory, primary motor, and premotor areas when the input is actively used in guiding behavioral tasks?

Recently, we found that the timing of hippocampal sharp-wave ripple events is modulated by the respiratory cycle. These findings represent a possible neuronal mechanism for a direct influence of the respiratory cycle on memory function. We also found that cerebellum modulates the intrinsic rhythmicity of eupneic breathing in a way that would be consistent with a cerebellar role in coordinating the respiratory rhythm with other orofacial movements, such as swallowing. Another line of my research also points to a possible role of the cerebellum as a coordinator of rhythms. We recently published causal evidence for a cerebellar role in controlling the coherence of neural oscillations between prefrontal cortex and hippocampal CA1 region during the decision-making process in a spatial working memory task. In ongoing research, we continue to investigate neuronal mechanisms of cerebro-cerebellar interaction, focusing on the modulation of functional connectivity between forebrain areas.

Bio

Dr. Michaels is working with colleagues in the US and Canada to examine how medical schools assess humanistic traits in their applicants. She also has an interest in promoting wellbeing in medical students and developing resources for mental health services and addressing food insecurities.

Teaching Summary

Lecturer in the Neurological Medicine Course; Lab instructor for Human Anatomy sessions.

Mentoring/Advising: All medical students on campus; several undergraduates preparing for professional school and early career faculty at our school. 

Research Summary

Dr. Nordgren's research interest focuses on development of innovative educational methods and resources for health professions education. In particular, her work emphasizes the importance of active learning strategies and builds on the framework of Guided Discovery Learning.

Bio

Dr. Regal was named the Co-Interim Regional Campus Dean of the University of Minnesota Medical School, Duluth Campus. She became active in this role on April 19, 2021 through Summer 2022.

Research Summary

The overall goals of my research program involve understanding basic immune mechanisms of cardiopulmonary disease. I have a long-standing interest in the complement system as a mediator of adverse events in disease states such as anaphylaxis, asthma and most currently pregnancy-induced hypertension. These interests have also involved defining mechanisms of pulmonary immunotoxicity of small molecule workplace allergens such as trimellitic anhydride. My research approach involves experimentation at the molecular, biochemical and physiological levels using animal models of disease. Current research projects include:

Pregnancy-induced Hypertension Preeclampsia and related hypertensive disorders of pregnancy affect ~10% of all pregnancies in the United States, significantly impacting the health of both mother and child. The initiating event of preeclampsia involves impaired blood flow to the placenta and the end result for the mother is high blood pressure and protein in the urine, along with growth restriction in the fetus. During pregnancy, the immune system including the plasma complement system, is tightly regulated to allow fetal survival. In women with preeclampsia the complement system is excessively activated, and our long-term goal is to determine the therapeutic utility of manipulating the complement system to prevent preeclampsia or minimize consequences for the mother and child. We hypothesized that complement system activation and white blood cell recruitment lead to hypertension in the mother and growth restriction in the fetus. Thus, we are manipulating the complement system and white blood cell function in a model of placental ischemia induced high blood pressure to determine the critical mechanisms responsible for the pregnancy complications. Our most recent studies are defining the role of natural antibody and the B lymphocyte in initiating complement activation in vivo, and assessing the importance of endogenous complement regulators in limiting the activation.

Dr. Regal's lab is currently funded through the National Heart Lung and Blood Institute of NIH and the American heart Association. 
 

Professional Associations

• Director, AHC Women's Mentoring Program
• Director, AHC Duluth Research Seminar Series
• Editorial Board, Hypertension
• Editorial Board, Toxicological Sciences
• Associate Editor, Journal of Immunotoxicology
• Fellow, Academy of Toxicological Sciences

Teaching Summary

Chemotherapy of Infection; Anti-inflammatory Drugs; Drugs for Pulmonary Disorders
Mentoring/Advising: undergraduates, graduate & post-doctoral fellows
 

Research Summary

Our group studies colorectal cancer, the third most common cause of cancer deaths in the US. Colorectal cancer arises from the intestinal epithelial stem cell compartment. The stem cell compartment regulates the balance of proliferation, differentiation and cell death that maintains the epithelial layer lining the intestinal lumen. Disruption of this balance leads to colon cancer. Our research is aimed at understanding factors that cause cancer-causing disruption of the stem cell compartment.

A series of studies by our group identified two genes, KCNQ1 and CFTR, as colorectal cancer tumor suppressor genes. Initially, these genes were identified as a candidate colorectal cancer driver genes in a Sleeping Beauty transposon-mediated forward genetic screen. In follow-up studies, targeted intestinal-specific deletion of Cftr and Kcnq1 in the Apc^Min mouse model of intestinal tumorigenesis resulted in significantly more intestinal tumors. Most important, studies of human colon tumors demonstrated that diminished expression of either KCNQ1 or CFTR is associated with poorer prognosis.

KCNQ1 and CFTR are both expressed in the intestinal epithelial stem cell compartment. They encode ion channels expressed at the cell surface. As such, they in a position to influence the cellular processes that maintain the stem cell compartment. Our current research focuses on understanding how deficiency for KCNQ1 and CFTR disrupts the stem cell compartment and promotes the development of poor prognosis colon cancer.

Teaching Summary

Cancer biology, colorectal cancer, intestinal epithelial stem cell.

Mentoring/Advising: undergraduate researchers, MS and PhD candidates, postdoctoral fellows.

Research Summary

My research program investigates the intersections between the worlds of perinatal biology and cellular immunology to identify and understand underlying mechanisms that contribute to the development of maternal diseases. My work currently focuses on identifying and developing novel, personalized cellular immunotherapy approaches to treat and prevent hypertensive diseases in pregnancy. Other work in the lab focuses on the impact of maternal diseases on the future health of mom. The development of safe, novel therapeutic interventions for maternal diseases are vital to improving women's health in both the short-term and the long-term.

Further, as an under-represented minority and a first-generation college graduate, teaching and inspiring others to go into science is a priority in my personal and professional lives. I have had exceptional mentors throughout my training. These mentors and the acceptance of my own personal journey has inspired me to seek opportunities to mentor other diverse learners throughout my career. I strive to provide the same high level of mentorship that I have received to those I train to ultimately provide a more inclusive and equitable representation in science and medicine.
 

Publications

Research Summary

Research in the Shaw lab focuses on the interaction between three cell types in the tumor microenvironment (carcinoma cells, fibroblasts and myeloid cells) in mediating tumor metastasis. Our research has shown that secreted factors from myeloid cells encourage the invasion of fibroblasts (leader fibroblasts); and this directly increases carcinoma cell invasion. Although we have identified some proteins that mediate this activity, our current work is examining the roles of RNAs in exosomes. Our work uses live cell microscopy to image cells in 3-dimensional constructs. Our current work uses CellMate3DTM, a chemically-defined tissue-like microenvironment composed of hyaluronic acid and chitosan (BRTI Life Sciences). BRTI Life Sciences is a local biotech company located in Two Harbors, MN and I work closely with BRTI researchers to develop novel therapeutics and cultivate local industry.

Service Summary

Area Editor
National Board of Medical Examiners, approximately 65 hours spent per year. (November 2019 - Present).
Review questions for the NBME Physiology Exam

Grant Reviewer
Department of Defense Breast Cancer Research Program, United States, approximately 130 hours spent per year. (December 2018 - Present).

Service to the University of Minnesota
Member, Clinical Competency Committee #3, approximately 48 hours spent per year. (May 23, 2022 - Present).

Member, Medical School Scholastic Standing Committee, approximately 15 hours spent per year. (November 29, 2021 - Present).
Overview Committee created to oversee COSSS (TC) and SSC (DU).

Member, Duluth Scientific Foundations Committee, approximately 30 hours spent per year. (2021 - Present).
Department

Member, Biomedical Sciences Curriculum Committee, approximately 30 hours spent per year. (October 10, 2018 - Present).