Faculty

Bio

I have been at the University of Minnesota since 2012, and Director of the Neuromuscular Medicine Fellowship Program since 2017. My priorities include offering exceptional clinical care for patients with neuromuscular diseases, providing the most up-to-date neuromuscular education to students, residents, and fellows, and researching new therapeutic options for neuromuscular conditions that represent unmet medical needs, with a specific focus on myopathies of adults and ALS.

Clinical Summary

• ALS Peripheral neuropathy
• Neuromuscular junction disorders
• Muscular dystrophies of adults
• Acquired myopathies of adults

Bio

Dr. McLoon received her PhD from the Department of Anatomy at the University of Illinois Medical Center, followed by postdoctoral studies with Dr. Ray Lund at the University of Washington and Medical University of South Carolina. She is a tenured Professor in the Department of Ophthalmology and Visual Neurosciences. She studies pharmacologic approaches to the treatment of eye movement disorders in children, specifically strabismus and nystagmus. She is focused on the cell biology and muscle stem cell populations within the muscles that move the eyes in the orbit, the extraocular muscles, to understand their sparing in diseases such as Duchenne muscular dystrophy and what goes awry in eye movement disorders. Recently she has added an interest in sex differences in retinal function and how this relates to neuropsychiatric disease.

Expertise
Strabismus, nystagmus, muscle stem cells, muscle injury, muscle regeneration, craniofacial muscles, neurotrophic factors

Research Summary

My laboratory focuses on understanding the potential mechanisms for two types of eye movement disorders: strabismus and nystagmus. Untreated these result in decreased visual acuity. Both involve the ocular motor system and the specialized skeletal muscles that move the eye, the extraocular muscles (EOM). We focus on the ability of retrogradely transported neurotrophic factors to alter the function and structure of the ocular motor system with the goal of developing a permanent therapeutic approach for these movement disorders. We have used RNAseq data to identify potential new therapeutic targets for development of treatments.

A second focus is the study of the muscle stem cell populations in the EOM that cause their differential sparing in degenerative disorders such as muscular dystrophy and amyotrophic lateral sclerosis. We have identified a specific stem cell, expressing Pitx2, which we have implicated in this differential sparing. Further work will focus on using these stem cells to prevent limb muscle degeneration in these currently untreatable diseases.

Finally, we have started a new project looking at the electroretinogram (ERG) in various mouse models of disease. Our recent studies show a significant difference in ERG characteristics in a mouse model of schizophrenia compared to controls, suggesting a specific method by which differences in the brain can be measured in the retina.

Research interests:
Development of pharmacologic treatments for strabismus and infantile nystagmus syndrome
Extraocular muscle cell biology
Sparing of the extraocular muscles in muscular dystrophies
Molecular control of extraocular muscle properties and how these are affected in strabismus and nystagmus
Sex differences in the electroretinogram

Teaching Summary

Courses
NSC 5203 Neuroscience of Vision
NSC 8321 Career Skills for Neuroscientists

Bio

Joseph M. Metzger, Ph.D., is the Maurice Visscher Land-Grant Chair of Physiology and Professor and Head of Integrative Biology and Physiology at the University of Minnesota Medical School. The Metzger laboratory uses molecular and integrative biomedical approaches for mechanistic investigations of heart and skeletal muscle function, with the long-range goal of translating these findings to new therapies and treatments for acquired and inherited heart and muscle diseases.
Metzger Lab Mission Statement: We seek mechanistic insights into normal and diseased cardiac and skeletal muscle function. Our overarching goal is to translate basic science discoveries into potential therapeutic strategies to combat inherited and acquired forms of heart and muscle diseases. Lab projects embrace individuality, emphasize cooperation and collaboration, and encompass a standard of excellence to all that we do as individual researchers and as a laboratory. Our guiding principles are to treat others with respect and courtesy, to maintain the lab in a collegial, safe and professional environment, and to work each day to the fullest of our capabilities.
Metzger received a Bachelor's degree in Natural Science from Saint John's University, Collegeville, Minnesota (1980), a Master's degree in Biology and Exercise Physiology from Ball State University, Muncie, Indiana (1982), a Ph.D. degree in Biology/Physiology under the mentorship of Dr. Robert Fitts from Marquette University Milwaukee, Wisconsin (1985), and performed post doctoral studies with Dr. Richard Moss at the University of Wisconsin, Madison, Wisconsin (1991). His lab designed and implemented a cardiac muscle-cell system that allows the transfer of genes into heart cells in order to assess the impact of those genes on the production of force and motion, the major function of cardiac muscle cells. The approach has the advantage of shedding light on the primary role of a normal or mutated gene in an otherwise normal muscle cell.
Metzger's findings have been published in top peer journals including Nature, Science, Nature Medicine, the Journal of Clinical Investigation, and the Proceedings of the National Academy of Sciences. This research is funded by the National Institutes of Health (NIH), the American Heart Association, the Muscular Dystrophy Association, and the Federation to Eradicate Duchenne, and has opened the path to treatment for a variety of heart and muscle diseases.

Research Summary

We are a mechanistically driven biomedical research lab focused on the form and function of heart and skeletal muscle in health and disease. We use molecular and integrative biomedical approaches for mechanistic investigations of heart and skeletal muscle function, with the long-range goal of translating these findings to new therapies and treatments for acquired and inherited heart and muscle diseases.Integrative systems biology of cardiac and skeletal muscle function Gene therapy, Gene and Base Editing Synthetic chemistries as membrane stabilizers Transgenic models of heart and muscle diseases Molecular mechanisms of sarcomere function Human iPS cell cardiac and skeletal muscle

Bio

Dr. Miller completed his Pediatric residency (2000) and Pediatric Endocrinology fellowship (2003) at the Mayo Clinic. He is a Professor in Pediatric Endocrinology, and has been a member of the division since 2003. Dr. Miller has an interest in the role of the growth hormone (GH)/insulin-like growth factor (IGF) system in normal and abnormal growth in children. Additionally, he is interested in the growth and development of children following adversity including cancer and its therapies, fetal alcohol exposure, and international adoption. Dr. Miller is also interested in the endocrine aspects of abnormal glycosylation in children with Congenital Disorders of Glycosylation. Lastly, Dr. Miller is also interested in Achondroplasia and other skeletal dysplasia conditions.

Research Summary

Growth, Puberty and Bone Disorders, Rare Disease

Clinical Summary

General Disorders of Growth and Puberty; Endocrine problems in cancer and bone marrow transplant survivors; Growth and pubertal disorders in children who have experienced early adversity including International Adoption, Fetal Alcohol Syndrome, Prematurity and Small for Gestational Age; Congenital Disorders of Glycosylation; Adrenoleukodystrophy; Fanconi Anemia; Neurofibromatosis; Prader Willi Syndrome; Russell-Silver Syndrome; Skeletal Dysplasia including Achondroplasia.

Research Summary

Advanced imaging of brain tumors
Adrenoleukodystrophy
Inherited diseases of the brain and spine
Medical Education
Integrating Technology with Health Care

Clinical Summary

Injections for pain relief
Intraarterial chemotherapy delivery for brain tumors and retinoblastoma
Imaging of metabolic and inherited disorders of children
Brain tumor imaging

Bio

Laura Niedernhofer, MD, PhD, joined the University of Minnesota in July 2018 to direct the new Institute on the Biology of Aging & Metabolism (iBAM) and Medical Discovery Team on the Biology of Aging. She is a professor in the Department of Biochemistry, Molecular Biology and Biophysics. Dr. Niedernhofer’s expertise is in DNA damage and repair, genome instability disorders, cellular senescence and aging. Her research program is centered on studying fundamental mechanisms of aging and developing therapeutics to target them. Her research program implements a murine model of a human progeroid syndrome caused by a defect in DNA repair. She contributed to the discovery of a new class of drugs called senolytics. Dr. Niedernhofer has served on study section for NCI, NIEHS and NIA. She has been awarded for research in aging, cancer and environmental health science. 

Research Summary

Dr. Niedernhofer's research career has been dedicated to investigating the impact of DNA damage on the structure of DNA, cell function and organism health. The DNA in each of our cells is damaged thousands of times per day by exposure to environmental factors, dietary components, chemotherapeutic agents and even endogenous by-products of normal metabolism. Studying patients with rare diseases caused by inherited defects in DNA repair provides important insight into the consequences of DNA damage. These patients have a dramatically increased risk of cancer and age prematurely. The Niedernhofer Lab has engineered mouse models of these genome instability syndromes as a sensitive tool to test hypotheses about how DNA damage promotes cancer and aging.

Research Summary

Dr. Orr is professor and the James Schindler and Bob Allison Ataxia Chair in Translational Research in the department, directs the Institute of Translational Neuroscience, and is a member of the Division of Molecular Pathology and Genomics.  His research is focused on the molecular genetics of neurodegenerative diseases, principally the autosomal dominant form of spinocerebellar ataxia (SCA1). Patients usually develop SCA1 in mid-life. They experience loss of motor coordination and develop slurred speech, spasticity, and cognitive impairment. These symptoms arise from the loss of Purkinje cells and damage to other nerve cells in the brain's cerebellar cortex. Orr and his colleagues cloned the SCA1 gene and found that the disease is caused by the expansion of an unstable, repeated cytosine-adenine-guanine (CAG) sequence in DNA. The length of the trinucleotide repeat is associated with when symptoms develop.The trinucleotide repeat encodes an expanded polyglutamine tract, an important step in disease pathogenesis. Orr and his colleagues established the first transgenic mouse model for SCA1 with which they were able to induce ataxia with Purkinje cell features characteristic of SCA1 by inserting CAG repeats. The model has helped his team understand how the SCA1 mutant polyglutamine protein, ataxin-1, moves from the cytoplasm into the nucleus of Purkinje cells where together with other protein complexes it causes Purkinje dendrites to atrophy. They found that phosphorylation of a specific ataxin-1 serine results in greater stabilization of the mutant protein, which alters the normal ratio of stabilized versus degraded protein and results in aberrant binding and disease.In the experimental therapeutics arena, Orr and colleagues are using RNA interference (RNAi) and adeno-associated virus (AAV) vectors as a delivery system to reduce ataxin-1 expression in Purkinje cells. Orr also working with a company that has developed anti-sense oligonucleotide chemistry. Anti-sense oligonucleotides act at the level of messenger RNA before proteins are produced. Delivering drugs to the central nervous system is difficult. Delivering molecular therapies to the deep cerebellar nuclei of the cerebellar cortex, where Purkinje neurons cluster and terminate, is a significant challenge. Orr's University colleagues have experience using AAV vectors to deliver genes to Purkinje cells. When human trials begin, the hope is that a sufficient number of therapeutic molecules will be taken in by Purkinje cell terminals and transferred to the cell bodies to be beneficial to patients.

Publications

• Liu CJ, Williams KE, Orr HT, Akkin T. Visualizing and mapping the cerebellum with serial optical coherence scanner. Neurophotonics. 2017 Jan;4(1):011006.
• Rubinsztein DC, Orr HT. Diminishing return for mechanistic therapeutics with neurodegenerative disease duration?: There may be a point in the course of a neurodegenerative condition where therapeutics targeting disease-causing mechanisms are futile. Bioessays. 2016 Oct;38(10):977-80. doi: 10.1002/bies.201600048.
• Ingram M, Wozniak EA, Duvick L, Yang R, Bergmann P, Carson R, O'Callaghan B, Zoghbi HY, Henzler C, Orr HT. Cerebellar Transcriptome Profiles of ATXN1 Transgenic Mice Reveal SCA1 Disease Progression and Protection Pathways. Neuron. 2016 Mar 16;89(6):1194-207. doi: 10.1016/j.neuron.2016.02.011.
• Malhotra D, Linehan JL, Dileepan T, Lee YJ, Purtha WE, Lu JV, Nelson RW, Fife BT, Orr HT, Anderson MS, Hogquist KA, Jenkins MK.
  Tolerance is established in polyclonal CD4(+) T cells by distinct mechanisms, according to self-peptide expression patterns.
  Nat Immunol. 2016 Feb;17(2):187-95. doi: 10.1038/ni.3327.

Bio

The Pacak laboratory investigates mechanisms that lead to mitochondrial dysfunction in a variety of disease settings using differentiated patient-derived induced pluripotent stem cells (iPSCs), mouse models, and adeno-associated virus (AAV) mediated gene delivery systems.

Research Summary

The Pacak laboratory is focused on identifying common mechanisms of disease related to mitochondrial function that can be augmented through gene therapies. The lab uses differentiated iPSCs and a variety of in vivo models to pursue these investigations.

Bio

Our laboratory has a long-term interest in understanding the molecular mechanisms controlling lineage-specific differentiation of pluripotent stem cells (PSC), which has led to the efficient generation of  PSC-derived myogenic progenitor cells endowed with in vivo regenerative potential. Current research projects focus on the effect of the environment on the engraftment and maturation of PSC-derived myogenic progenitors, the development of allogeneic and autologous cell therapy for muscular dystrophies (MD), and application of MD patient-specific iPSC-derived muscle derivatives for disease modeling and drug discovery.

Creative Activity Summary

Full list of publications at Experts@Minnesota or PubMed.

1. Baik J, Ortiz-Cordero C, Magli A, Azzag K, Crist SB, Yamashita A, Kiley J, Selvaraj S, Mondragon-Gonzalez R. Perrin E, Maufort JP, Janecek JL, Lee RM, Stone LH, Rangarajan P, Ramachandran S, Graham ML, & Perlingeiro RCR. (2023). Establishment of skeletal myogenic progenitors from non-human primate induced pluripotent stem cells. Cells, 12(8), 1147; https://doi.org/10.3390/cells12081147.
2. Singh BN, Yucel D, Garay BI, Tolkacheva EG, Kyba M, Perlingeiro RCR, van Berlo J, & Ogle BM, (2023) Proliferation and Maturation: Janus and the art of engineered cardiac tissue. Circulation Research, 132(4):519-540.  PMCID: PMC9943541.
3. McKenna DH & Perlingeiro RCR, (2023) Development of allogeneic iPS cell-based therapy: from bench to bedside. EMBO Molecular Medicine, 15(2):e15315. PMCID: PMC9906386.
4. Azzag K, Bosnakovski D, Tungtur S, Salama P, Kyba M, & Perlingeiro RCR, (2022) Transplantation of pluripotent stem cell-derived myogenic progenitors counteracts disease phenotypes in a mouse model of FSHD. NPG Regenerative Medicine,  7(1):43. PMCID: PMC9440030.
5. Garay BI, Givens S, Stanis N, Magli A, Yücel D, Abrahante JE, Goloviznina NA, Soliman HAN, Dhoke NR, Baik J, Kyba M, van Berlo JH, Ogle B, & Perlingeiro RCR, (2022) Inhibition of mitogen-activated protein kinase pathway enhances maturation of human iPSC-derived cardiomyocytes. Stem Cell Reports. 17(9):2005-2022. PMCID: PMC9481895.
6. Kim H, & Perlingeiro RCR, (2022) Generation of human myogenic progenitors from pluripotent stem cells for in vivo regeneration. Cellular and Molecular Life Sciences. 8;79(8):406. doi: 10.1007/s00018-022-04434-8. PMCID: PMC9270264.
7. Ortiz-Cordero C, Bincoletto, C, Dhoke N, Selvaraj S, Magli A, Zhou H, Kim D-H, Bang AG, & Perlingeiro RCR, (2021), Defective autophagy and increased apoptosis contribute toward the pathogenesis of FKRP-associated muscular dystrophies. Stem Cell Reports. 16(11):2752-2767. PMCID: PMC8581053.
8. Dhoke N, Kim H, Selvaraj S, Oliveira NAJ, Azzag K, Tungtur S, Ortiz-Cordero C, Kiley J, Lu QL, Bang A, & Perlingeiro RCR, (2021), A universal gene correction approach for FKRP-associated dystroglycanopathies to enable autologous cell therapy. Cell Reports. 36(2):109360. PMCID: PMC8327854.
9. Ortiz-Cordero C, Magli A, Dhoke N, Kuebler T, Selvaraj S, Oliveira NA, Zhou H, Sham YY, Bang AG, & Perlingeiro RCR, (2021), “NAD+ enhances ribitol and ribose rescue of α-dystroglycan functional glycosylation in human FKRP-mutant myotubes”. Elife, 2021 10:e65443. PMCID: PMC7924940
10. Ortiz-Cordero C, Azzag K, & Perlingeiro RCR, (2021), “Fukutin-Related Protein: from Pathology to Treatments”. Trends in Cell Biology, 31:197-210. PMID: 33272829 (cover article).
11. Kim H, Selvaraj S, Kiley J, Azzag K, Garay BI, & Perlingeiro RCR, (2021), “Genomic safe harbor expression of PAX7 for the generation of engraftable myogenic progenitors”. Stem Cell Reports, 16:10-19.PMCID: PMC7815936
12. Baik J, Felices M, Yingst A, Theuer, CP, Verneris MR, Miller JS, & Perlingeiro RCR,(2020), “Therapeutic effect of TRC105 and decitabine combination in AML xenografts”. Heliyon, 6(10):e05242. PMCID: PMC7566100.
13. Incitti T, Magli A, Jenkins J, Lin K, Yamamoto A and Perlingeiro RCR, (2020), “Pluripotent stem cell-derived skeletal muscle fibers preferentially express oxidative myosin heavy-chain isoforms: new implications for Duchenne Muscular Dystrophy”. Skeletal Muscle, 10(1):17. PMCID: PMC7268645
14. Azzag K, Ortiz-Cordero C, Oliveira NAJ, Magli A, Selvaraj S, Tungtur S, Upchurch W, Iaizzo PA, Lu QL and Perlingeiro RCR, (2020) “Efficient Engraftment of Pluripotent Stem Cell-Derived Myogenic Progenitors in a Novel Immunodeficient Mouse Model of Limb Girdle Muscular Dystrophy 2I”. Skeletal Muscle, 10(1):10. PMCID: PMC7175515.
15. Selvaraj S, Mondragon-Gonzalez R, Xu B, Magli A, Kim H, Lainé J, Kiley J, McKee H, Rinaldi F, Aho J, Tabti N, Shen W, & Perlingeiro RCR, (2019) “Screening identifies small molecules that enhance the maturation of human pluripotent stem cell-derived myotubes”. eLIFE, 8. pii: e47970. PMCID: PMC6845233.
16. Selvaraj S, Dhoke N, Kiley J, Aierdi AJM, Mondragon-Gonzalez R, Killeen G, Oliveira VKP, Tungtur S, Munain AL & Perlingeiro RCR, (2019) “Gene Correction of Limb Girdle Muscular Dystrophy Type 2A Patient-Specific iPS Cells for the Development of Targeted Autologous Cell Therapy”. Molecular Therapy,27:2147-2157. PMCID: PMC6904833.
17. Selvaraj S, Kyba M & Perlingeiro RCR, (2019) “Pluripotent Stem Cell-Based Therapeutics for Muscular Dystrophies” Trends in Molecular Medicine. 25:803-816. PMCID: PMC6721995. (cover article)
18. Mondragon-Gonzalez R, Azzag K, Selvaraj S, Yamamoto A & Perlingeiro RCR, (2019) “Transplantation studies reveal internuclear transfer of toxic RNA in engrafted muscles of myotonic dystrophy 1 mice”. eBioMedicine. 47:553-562. PMCID: PMC6796515.
19. Magli A, Baik J, Pota P, Ortiz Cordero C, Kwak IY, Garry DJ, Love PE, Dynlacht BD and Perlingeiro RCR, (2019) “Pax3 cooperates with Ldb1 to direct local chromosome architecture during myogenic lineage specification”. Nature Communications, 10:2316. PMCID: PMC6534668.

Full list of publications at Experts@Minnesota or PubMed.

Bio

Dr. Polly is a professor and chief of spine surgery in the Department of Orthopedic Surgery. He holds the James W. Ogilvie Chair and the Catherine Mills Davis Land Grant Chair in Biomechanical Engineering. He is nationally and internationally recognized for biomechanics and outcomes research. He cares for complex pediatric and adult spine conditions and is well known for scoliosis research.

Expertise

• Orthopedics
• Spine and Scoliosis
• Spine Surgery
• Pediatric Orthopedics

Awards & Recognition

• Best Doctors in America®: 2009-2010, 2011-2012, 2013, 2015
• America's Top Doctor: 2004-2008, 2010-2017
• American Society of Spine Radiology (ASSR) Best Oral Paper Presentation in the Diagnostic Spine Category: 2016
• Value Award Best Paper at North American Spine Society (NASS): 2015
• Catherine Mills Davis Land Grant Chair in Biomechanical Engineering in Orthopaedic Surgery, University of Minnesota: 2014
• Co-author Hibbs Award Finalist , Minimum 20-Year Radiographic Outcomes for Treatment of Adolescent Idiopathic Scoliosis: Results from a Novel Cohort of US Patients Scoliosis Research Society, Anchorage, AK: 2014
• Recipient of the 2011 Charles D. Ray Award for Best Clinical Paper-Radiographic Comparison of Lateral Fusion (LLIF) vs. ALIF vs. TLIF vs. Posterior Fusion: Analysis of Segmental Sagittal Contour Change, (ISAS), Las Vegas, NV: 2011.
• Winner-White Cloud Award-Best Clinical Paper (co-author) International Meeting on Advanced Spine Techniques (IMAST) 16th annual meeting, Vienna, Austria: July 15-18, 2009.
• Nominee co-author Louis A. Goldstein Award best clinical poster, Scoliosis Research Society Annual Meeting, Edinburgh, Scotland: September 4-8-2007.
• Outstanding Paper, Resident/Fellow Award: Eastern Orthopaedic/Southern Orthopaedic Association Annual Meeting, Dublin, Ireland. Straight-Forward versus Anatomic Trajectory of Thoracic Pedicle Screws: A Biomechanical Model. (Senior Author): 2003
• Outstanding Poster Award, 17th annual meeting of the North American Spine Society: 2002
• Finalist Hibbs' basic science award paper, Scoliosis Research Society annual meeting: 2002
• Recipient of the General Claire L. Chennault award as the outstanding teacher at Walter Reed Army Medical Center: 2002
• Recipient of the David C. Wherry Award in emerging technologies from the Uniformed Services University of the Health Sciences: 2002

Publications

View Dr. Polly's Publications on PubMed

Professional Associations

• President of the Scoliosis Research Society: 2014-2016
• Member of Board of Councilors for the American Academy of Orthopaedic Surgeons (AAOS): 2010-Present
• Member of Board of Specialty Societies for the American Academy of Orthopaedic Surgeons (AAOS): 2015-Present
• Minnesota Orthopaedic Society Board of Directors: 2010-Present 

Clinical Summary

Board Certifications

American Board of Orthopaedic Surgery

Clinical Interests

Spine (pediatric and adult); Scoliosis; Spinal tumors; Spine degenerative disease

Bio

Dr. Paul Robbins is a Professor of Biochemistry, Molecular Biology and Biophysics and the Associate Director of the Institute on the Biology of Aging and Metabolism (iBAM) and the Medical Discovery Team on the Biology of Aging at the University of Minnesota.

He was one of the first to identify enhancer elements that regulate transcription at a distance, the first to show that the retinoblastoma tumor suppressor regulates transcription and the first to develop gene therapies for autoimmune disease including an ongoing clinical trial for osteoarthritis. More recently, he was part of a collaborative team that was the first to identify senotherapeutic compounds, able to reduce the senescent cell burden and extend healthspan and lifespan in mouse models, that are in more than 15 clinical trials for age related diseases and conditions.

Research Summary

The pathways important for driving autoimmune and inflammatory diseases as well as age related degeneration are surprisingly similar. For example, inhibition of the transcription factor NF-?B is therapeutic in mouse models of autoimmunity and inflammation as well as Duchenne muscular dystrophy and aging. Similarly, inhibition of IL-1ß signaling by gene transfer of the IL-1 receptor antagonist protein is therapeutic in multiple models of diseases. The Robbins Lab is developing novel approaches to treat autoimmune (type 1 diabetes, rheumatoid arthritis), inflammatory (inflammatory bowel disease, delayed type hypersensitivity) and age-related degenerative diseases using biologics and small molecules. The therapeutic approaches being developed include: 1) AAV mediated gene transfer of anti-inflammatory or immunosuppressive agents; 2) Peptide and small molecule inhibitors of the transcription factor of NF-?B; 3) Novel osteogenic peptides; 4) Adult stem cells; 5) Microvesicles (exosomes) derived from immunoregulatory or stem cells able to block inflammation or promote regeneration; and 6) Identification of drugs able to reverse cellular senescence for improving healthy aging. Although the majority of the studies are being performed in mouse models of disease, approaches to treat osteoarthritis by intra-articular AAV-mediated gene transfer and Duchenne muscular dystrophy by systemic treatment with a NF-?B inhibitory peptide will soon be entering the clinic.