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Cell Adhesion and Metastasis

• Panos Z. Anastasiadis, Ph.D., Professor of Cancer Biology, Director Cell Adhesion and Metastasis Lab, and Cell Biology Program Director, Mayo Clinic Cancer Center

  Our basic research program is focused on signaling events that regulate cell-cell adhesion or cell migration/invasion and transformed cell growth. In particular, we are interested in elucidating the role of cadherins and their intracellular binding partners, the catenins, in human cancer. We also study polarity complexes and Rho family GTPases, which together with the cadherin adhesion complex play critical roles in regulating cellular architecture and function. Through a better understanding of the mechanisms underlying cell adhesion and polarity, we hope to gain insights into the process of tumor cell migration and invasion and identify novel targets for therapy of metastatic cancers. Our translational research focuses on functional genomics with an emphasis on treatment options for aggressive cancers including brain gliomas, serous endometrial carcinomas, as well as lung, liver, and breast cancer.

Nanotechnology in Medicine

• Santanu Bhattacharya, Ph.D., Assistant Professor of Biomedical Engineering, Mayo Clinic College of Medicine and Science

  Santanu Bhattacharya, Ph.D., has multidisciplinary training and research expertise in nanotechnology, biophysics and cancer biology. Nanotechnology and the use of nanostructures have enormous promise in biomedical applications. Interests and investments in the application of nanotechnology in medicine are growing and progressing at a rapid pace, bringing a new field of research — nanomedicine.

Cancer Biology and Translational Oncogenomics

• John “Al” Copland III, Ph.D., Professor of Cancer Cell Biology & Oncogenomics, Mayo Clinic Department of Cancer Biology

  John A. Copland III, Ph.D., leads the Cancer Biology and Translational Oncogenomics Laboratory at Mayo Clinic's campus in Florida. Research in the lab is aimed at better understanding the mechanisms and pathways of carcinogenesis and tumor progression in order to develop novel, synergistic cancer therapies. Discoveries have led to clinical trials and development of novel therapeutic agents. Currently, two trials from discoveries made in our lab are anticipated in 2024. A novel TSHR CART therapy for metastatic thyroid cancer has been developed with preclinical data demonstrating durable response. We have developed a novel small molecule inhibitor called SSI-4 (now MTI-301) that binds to and blocks the biological activity of stearoyl CoA desaturase one (SCD1) protein. SCD1 is the rate limiting enzyme converting saturated fatty acids (SFAs) to monounsaturated fatty acids (MUFAs). SSI-4 has been licensed to Modulation Therapeutics Inc (MTI) and is expected to be in a Phase 1 clinical trial in early 2024. All of this work is achievable through multiple productive collaborations. Additionally, the laboratory develops novel patient tumor derived preclinical models to provide mechanistic insights and to test novel therapeutics in combination towards antitumor synergy.

Bacterial adaptation to antibiotic exposure

• Terri N. Ellis, Ph.D., Associate Professor of Biology, �ϰ������� Biology Department

  Research in my lab focuses on the outer surface of the bacterial pathogen Klebsiella pneumoniae. This bacterial species is the third most common cause of nosocomial (hospital acquired) infections and is responsible for over 7,000 deaths per year in the United States. Alarmingly, up to 50% of these infections are resistant to most current antibiotics. Antibiotic resistance in bacteria is primarily a result of acquisition of well characterized resistance genes. However, resistance in Klebsiella commonly pairs acquisition of these resistance genes with other changes to the outer surface components as well. Examples of these changes include loss of porin transport genes and modifications to be secreted polysaccharide capsule. My research focuses on how these changes to the outer surface, that are associated with antibiotic resistance, impact the virulence of the bacteria and the progression of disease. While these changes have been well documented in the clinic, and can be used as diagnostic markers of resistance, their impact on bacterial pathogenesis have not been fully investigated.

Alzheimer’s disease and related neurodegenerative conditions

• Nilüfer Ertekin-Taner, M.D., Ph.D., Chair of the Department of Neuroscience, Professor of Neurology and Neuroscience, Mayo Clinic Florida

  Dr. Ertekin-Taner is a physician-scientist with seminal contributions to the field of Alzheimer’s disease and related neurodegenerative conditions. Her innovative, groundbreaking work combining complex genomics and deep endophenotypes is essential for the discovery of molecular disease mechanisms, new treatments and biomarkers for these devastating and currently incurable conditions.

   

  She has pioneered the endophenotype approach in genetic studies of Alzheimer’s Disease and related disorders (ADRD). Her laboratory applies leading-edge analytic approaches to integrate biological traits with multi-omics data to discover precision medicine therapies and biomarkers in ADRD. Dr. Ertekin-Taner is a PI of AMP-AD and Resilience-AD and was a PI of M²OVE-AD consortia and Florida Consortium for African American AD Studies (FCA³DS). She is the contact PI of the CLEAR-AD U19 Program comprising 13 sites and nearly 100 investigators focused on precision medicine biomarker and therapeutic discoveries.

   

  Dr. Ertekin-Taner has been continually funded by the National Institutes of Health and foundations, having served or serving as a Principal Investigator (PI) on 37 grants with total extramural grant support of about $80 million since 2008. Her lab is a leader in many national large-scale initiatives aiming to discover precision medicine therapies and biomarkers in Alzheimer’s and related disorders. Owing to her prolific, impactful work, Dr. Ertekin-Taner serves on numerous executive committees, advisory boards and is a frequently invited-speaker. Ertekin-Taner is the recipient of numerous awards including the 2022 Alzheimer’s Association Zenith Fellows Award. A board-certified neurologist, she continues to care for dementia patients. Dr. Ertekin-Taner is also a leader in education serving as Director and PI for Mayo Clinic Center for Clinical and Translational Science (CCaTS) KL2 Mentored Career Development Program, as Founding Chair of the Mayo Clinic Research Pipeline K2R Program and as a mentor to over 80 trainees to date from various career stages. 

  @DrNErtekinTaner, #NETanerLab

Molecular Mechanisms of Viral-induced Autoimmune Heart Disease

• DeLisa Fairweather, Ph.D., Professor, Mayo Clinic Departments of Cardiovascular Medicine and Immunology

  Viral attack of mitochondria in cells gives them a replicative advantage. The virus can be released in extracellular vesicles that contain content like microRNAs that influence the immune response to cause or prevent cardiac inflammation and heart failure. The Fairweather lab examines how these processes work to better understand the pathogenesis of disease, identify potential biomarkers to assist with diagnosis, and to harness the protective aspects of the response for regenerative medicine therapies.

Neurogenesis and Brain Tumors Laboratory - Studying the crosstalk between neural stem cells and glioblastoma cancer stem cells in humans

• Hugo Guerrero-Cazares, M.D., Ph.D., Associate Professor of Neurosurgery, Neuroscience, and Cancer Biology

  The team members of the Neurogenesis and Brain Tumors Laboratory are exploring the role of the neurogenic niche in the malignancy of glioblastoma and developing new ways to use human tissue to study cancer cell biology. We utilize cell and molecular biology approaches to study the interaction between glioblastoma cells and neural stem cells.  

Relationship between form and function of musculoskeletal systems

• M. Laura Habegger, Ph.D., Assistant Professor, �ϰ������� Department of Biology

  M.Laura Habegger, Ph.D., Assistant Professor, �ϰ������� Department of Biology

  My lab focuses on the relationship between form and function, mostly on the musculoskeletal systems of fishes. This area of study, called functional morphology, utilizes a wide arrange of techniques commonly used on the medical sciences such as CT scan renderings, 3D anatomical models and histology and it can be meshed with other disciplines such as engineering (biomechanics). Understanding how anatomical structures work not only can shed light into our understanding of vertebrate evolution but could also reveal valuable information on how nature solves common problems, ultimately igniting new ideas for manufactured products that could range from orthopedics devices to drag reduction mechanisms in airplanes.

Investigating Materials with Biomedical Applications

• Jason T. Haraldsen, Ph.D., Associate Professor, �ϰ������� Department of Physics

  All biomedical applications require material interactions, and understanding material interactions involve investigating electron motion. In this lab, we will examine the electronic and magnetic properties of materials with the set purpose of biomedical applications. In the Haraldsen lab, we use density functional theory and exact diagonalization to model materials and interactions on the quantum level to define and examine the properties that can be used for identification and utilization in biomedical applications. This includes, but is not limited to, DNA and biomolecule identification through nanopores and hypothermic magnetic materials for cancer treatments.

Biology of Aging

• John Hatle, Ph.D., Presidential Professor, �ϰ������� Department of Biology

  Our lab studies the physiology underlying the biology of aging. Most mortality in the US is due to age-related diseases (e.g., heart disease, cancers, diabetes, stroke), so our lab is part of the effort to understand aging, the common underlying risk factor for all these. Dietary restriction of protein extends lifespan and reduces reproduction in a broad range of species. We focus on the effects of dietary amino acids and their metabolic fate (burning for ATP, allocation to tissues), using our grasshopper study system. Dietary restriction of some specific amino acids (e.g., methionine, isoleucine) extends lifespan, and changes in the metabolic fate of amino acids may contribute to the longevity.

  �ϰ�������: Physiology of aging and reproduction in invertebrates

Molecular Mechanisms of Tumorigenesis

• Verline Justilien, Ph.D., Assistant Professor, Mayo Clinic Department of Cancer Biology

  The Justilien laboratory is interested in the molecular mechanisms involved in cellular transformation and cancer maintenance and progression. Our research is focused on: 1) investigating cancer stem cell mechanisms in tumorigenesis and the design and testing of rational and novel combination therapies to eliminate cancer stem cells; 2) elucidating oncogenic Ect2 signaling mechanisms that contribute to cancer and translating these mechanistic insights into better cancer treatment strategies; and 3) modeling of lung cancer to uncover signaling events critical for cells to progress through the tumorigenesis spectrum to identify therapeutically actionable targets to prevent the progression to malignant disease.

Biology in Age-related Cognitive Decline and Alzheimer’s Disease

• Takahisa Kanekiyo, MD, PhD, Associate Professor of Neuroscience, Mayo Clinic Jacksonville

  Kanekiyo lab studies the pathogenesis of age-related cognitive decline including Alzheimer’s disease (AD) and vascular cognitive impairment and dementia (VCID) using mouse models, human induced pluripotent stem cell (iPSC) models, and human biospecimens. Since APOE and ABCA7 are associated with AD risk, we actively investigate their roles in the diseases with a specific focus on lipid metabolism. In addition, as the accumulation of senescent cells is one of the major mechanisms triggering age-related phenotypes, we study contributions of senescence to neurodegenerative diseases. Goals of our translational research are to develop novel therapeutic strategies for neurodegenerative diseases through pharmacological approaches, gene therapy and stem cell-based regenerative medicine.

Protein Arginine Methyltransferase Targeted Cancer Therapeutics

• Bryan Knuckley, Ph.D., Professor, �ϰ������� Department of Chemistry & Biochemistry

  Methylation of proteins can alter protein structure, thereby altering binding interactions, and subsequently changing physiological functions and downstream regulatory pathways. In mammals, the formation of methylated protein-arginine is catalyzed by a family of enzymes termed Protein Arginine Methyltransferases (PRMTs) and several studies have demonstrated that overexpression of these enzymes leads to increased cell proliferation in cancers (e.g., prostate, breast, colon, and lung cancers).  The Knuckley Lab utilizes standard solid-phase synthesis, enzymology, and chemical biology to develop PRMT inhibitors as pharmaceutical-lead compounds for the treatment of these cancers.

Harnessing the Potential of Nature for Drug Discovery

• Amy L. Lane, Ph.D., Presidential Professor, �ϰ������� Department of Chemistry & Biochemistry

  Microorganisms are phenomenal chemists that produce a plethora of molecules (natural products) by using enzymes as their chemical synthesis tools. Natural products are a tremendous resource for drug discovery, and the majority of pharmaceuticals on the market today are derived from natural products. The Lane lab utilizes interdisciplinary tools from molecular biology, genetics, biochemistry, and organic chemistry to harness the potential of microorganisms as sources of drug candidates of the future.

Sensing the bacterial environment through mechanosensitive channels

• Hannah R. Malcolm, Ph.D., Associate Professor, �ϰ������� Department of Chemistry & Biochemistry

  The ability of a bacterium to sense and response to the environment is essential for their survival, the Malcolm Lab studies a family of ion channels in the membrane called mechanosensitive ion channels. In humans, mechanosensitive ion channels are responsible for hearing, touch sensation, proprioception, as well as many other biological processes. Bacterial ion channels have similar roles within the cell and present a potential novel antibiotic target. In order to discover how these channels function and could be an antibiotic target, the Malcolm Lab uses molecular biology techniques, standard biochemistry techniques, and patch clamp electrophysiology to directly observe these channels.

Drug Discovery for Neurodevelopmental Disorders

• Marie Mooney, Ph.D., Assistant Professor, �ϰ������� Department of Biology

  In the Mooney Laboratory for Informatics, Genomics, Health, and Technology (MoonLIGHT) we train the next generation of scientists to work collaboratively across fields to benefit human health. We specialize in studying neurodevelopmental disorders and have three areas of focus: Bioinformatics, Genetics, and Neuroscience. These all come together in a powerful way as we use our favorite model organism, the humble zebrafish (Danio rerio), to rapidly perform gene and drug discovery and collect genomic data.

Biochemistry of neuroinflammation

• Judith D. Ochrietor, Ph.D., Associate Professor, �ϰ������� Department of Biology

  The blood-brain barrier (BBB) and blood-retina barrier (BRB) are essential for protecting the integrity of the brain. Recent studies indicate that expression of the cell adhesion protein Basigin, found on both these barriers, is influenced by an inflammatory stimulus. The Ochrietor laboratory uses cell and molecular biochemistry techniques to investigate the role played by Basigin in the BBB and BRB and how that role changes in response to neuroinflammation.

Protease targets in tumor progression and metastasis

• Evette S. Radisky, Ph.D., Professor, Mayo Clinic Departments of Cancer Biology and Pharmacology; Associate Dean, Mayo Clinic Graduate School of Biomedical Sciences

  Research in our laboratory focuses on identifying novel avenues for therapeutic intervention in cancer progression and metastasis, focusing primarily on secreted proteases and protease inhibitors that play key roles in metastatic progression. Our research uses a combination of cell-based and mouse models of cancer, biochemical methods, x-ray crystallography, and computational modeling to identify specific proteases as therapeutic targets, elucidate mechanisms by which these enzymes drive tumor growth and progression, and develop novel selective protease inhibitors for intervention in proteolytic pathways.

Protein Aggregation in Neurodegenerative Disorders

• Wilfried Rossoll, Ph.D., Assistant Dean, Mayo Clinic Graduate School of Biomedical Science, Associate Professor, Neuroscience | Neuroscience (NSC), Biochemistry and Molecular Biology (BMB)

  Wilfried Rossoll, Ph.D., and his team study molecular mechanisms and cellular pathways of neurodegeneration in diseases characterized by increased protein aggregation, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD) and other proteinopathies. Dr. Rossoll’s laboratory uses state of the art high resolution microscopy, biochemistry, adeno-associated virus (AAV) mediated gene delivery, and innovative spatial and proximity proteomics approaches in neuronal cell culture, organotypic brain slice cultures, mouse models, human induced pluripotent stem cell-derived neurons, and human autopsy brain tissue, to better understand how pathological protein aggregations cause neurodegenerative diseases. The discovery of novel modifiers of protein aggregation allows them to target pathological phase transitions for therapy development. 

Mitochondrial Quality Control in Health, Aging, and Disease

• Wolfdieter Springer, Ph.D., Associate Professor, Department of Neuroscience, Mayo Clinic

  To maintain a healthy and functional mitochondrial network, the enzymes PINK1 and PRKN identify and label selectively damaged mitochondria with phosphorylated ubiquitin chains tagging them for degradation via the autophagy-lysosome system (mitophagy). Complete loss of either gene is linked to early-onset Parkinson’s disease, but impairments of the pathway seem to have much broader implications and contribute to stress, aging, and a variety of human disorders where mitochondrial or lysosomal dysfunctions emerge as shared leitmotif. The Springer lab uses human clinical and pathological samples as well as gene-edited iPSC-derived cell and in vivo animal models to determine mechanisms, develop and test disease and pharmacodynamics biomarkers, and explore the therapeutic potential of stimulating mitophagy in the context of aging and diseases of the brain and beyond.

Early Detection and Treatment of Pancreatic Cancer

• Peter Storz, Ph.D., Professor or Cancer Biology, Department of Cancer Biology, Mayo Clinic

  Research in the laboratory of Peter Storz, Ph.D., focuses on discovering events that lead to initiation and progression of pancreatic ductal adenocarcinoma (PDA), with the overall goals to better understand how this disease develops and to identify methods to target tumors at an earlier stage. To achieve this, they use genetic and orthotopic animal models, primary cells in 2D co-culture and 3D organoid culture, precision cut tissue slice culture, as well as human tissue and liquid biopsy samples. Their expertise is i) on how oncogenic mutations and stress signaling pathways synergize in initiating the tumorigenic process; and ii) on how pancreatic lesion and cancer cells crosstalk with their stromal environment, with a specific focus on macrophage populations.

Non-linear Optical Emission from Hybrid Bioplasmonic Metamaterials

• Gregory Wurtz, Ph.D., Professor and Chair, Department of Physics, �ϰ�������

  This research is to study the nonlinear optical properties of biomolecules when coupled to plasmonic metamaterials. In this project, suitable biomolecules will be selected and combined with plasmonic metamaterials designed to bolster the non-linear optical emission of the resulting hybrid. The coupled system will be fabricated and both their structural and optical response characterized. Targeted applications include biosensing, optical nanosources, and coherent emission.