PS121: Disease Mechanisms and Therapies (5 units) Rachelle H. Crosbie-Watson, Ph.D.

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1 PS121: Disease Mechanisms and Therapies (5 units) Rachelle H. Crosbie-Watson, Ph.D. Course Coordinator Teaching Associates Academic Coordinator Guest Faculty Instructors Prerequisite Courses Rachelle H. Crosbie-Watson, Ph.D. Professor of Integrative Biology And Physiology; Professor of Neurology UCLA Center for Duchenne Muscular Dystrophy Terasaki Life Sciences Building (TLSB) Tel: Office hours online on Adobe Connect Mondays 11am-12 pm Ronny Choe Cynthia Shu Courtney Young Zorica Scuric, Ph.D. The scientists, physicians, physical therapists, families, and members of the disabled community make significant (and completely voluntary) contributions to this course because they deeply value educating students in disease mechanisms and therapies. Their investment is what makes this a truly unique undergraduate experience. There are 15 experts that lecture in the course from the UCLA David Geffen School of Medicine as well as from academic institutes across the USA. Enjoy! Lower division undergraduate core courses in the life sciences at UCLA, this includes LS2, LS3, and LS4. Why is PS 121 a Great Elective Course for STEM Students? We have created a unique online course for which our teaching techniques are not captured in any currently available textbook. Our lectures were recorded as a short mini-lectures, a high-quality interactive video skits, that are arranged around our determined learning outcomes. Using modern educational tools as Learning glass and Pen Podium our faculties will bring to you an analysis of current, well-established scientific research that integrates across many disciplines. This approach is highly innovative and the PI and Key Faculty Instructors are working to create a textbook and other learning materials for the course. Why should you want to take Disease Mechanisms and Therapies Course? The goal of this course is to bring undergraduates into the real world of scientific research, therapy design, and clinical application. Students develop an understanding of personalized medicine and are able to apply that knowledge to other diseases and evaluate proposed therapeutic approaches to disease. The class is focused on using disease mechanisms as a pedagogical tool to develop higher order knowledge of basic scientific concepts since students are tasked with integrating concepts from genetics, molecular and cell biology, physiology, and biochemistry in order to create molecular solutions to the problem of inherited neuromuscular disease. Students in the life science and biochemistry majors are interested in human disease and the pursuit of professional degrees in medicine, nursing, pharmacology, physical therapy, patent/medicinal law, teaching, and research. The course appeals strongly to students professional goals and will advance their skills in each of these fields. 1

2 Disease Mechanisms and Therapies Course Fulfills the Diversity Course Requirement The topic of our course is inherited genetic muscular dystrophy that causes mental and physical disability leading to premature death in the early 20s. There is no cure for the muscular dystrophies and individuals are wheelchair reliant by ten. The disease affects all racial and ethnic groups equally. Students are being exposed to many facts and issues that disabled individuals are facing (see documentary video assignments), including accessibility issues that affect quality of life. Majority of our students are at the similar age as DMD men that are at the end of their life, and will make the impact on the life-perspectives of our students. The awareness of the health care disparities in how the quality of healthcare differs based on minority status, socioeconomic status, as well as minority group exploitation in clinical trials are addressed in the lectures. Protection and inclusion of minority groups in the context of clinical trials is evaluated. Students evaluate case studies of individuals with the same disease, but different disease outcomes that are due to lower quality health care to URM families, while majority groups receive standard of care. Students diversity awareness will be assessed weekly through planted Q&A during video lectures, weekly homework assignments, and topics discussed during synchronized discussion sections. Relevant diversity questions will be included in midterm and final exam. Also, students will be assigned a media assignment including a community research project about Duchenne Muscular Dystrophy in a video format. The course promotes a landscape of inclusiveness as exemplified by the faculty guest instructors (ten women and five men representing many different ethic and racial groups) as well as multiple documentaries featuring representatives of minority and low-income groups. Our online course creates a diverse, inclusive classroom that includes students at all UC campuses with a unique synchronous online discussion sections; students will be randomly dispersed in discussions) to connect across all UC campuses (see discussion sections organization). The goal is to stimulate communication and discussion between the students at UC Irvine and UC Riverside with students at UC Merced and UC Los Angeles and so on! Our course supports Bruin Allies for Duchenne (B.A.D.), the non-profit organization that was founded by a group of UCLA undergraduate students inspired by a face-to-face class taught by Dr. Rachelle Crosbie-Watson on Duchenne Muscular Dystrophy. The purpose of the organization is to broaden public awareness at UCLA and to the general public about this disorder. B.A.D. seeks to support families affected by Duchenne Muscular Dystrophy by providing practical and informational resources about DMD. The organization welcomes new members and could be reached by or its Facebook site: bruinalliesforduchenne@gmail.com PS121 course is supported by grants from PPMD (Parent Project Muscular Dystrophy), LGMD2I Foundation (Limb-girdle muscular dystrophy 2I), and Coalition Duchenne foundations. Parents and families with Duchenne children founded these organizations and act as advocacy groups involved in fundraising to support research, clinical trials and care for Duchenne patients. I. Course Organization: Lectures Discussion Sections Attendance Required 4-6 Mini-Lectures per week on course website Please use the following link: for technical issues, please contact Ava Arndt (Ava.arndt@ucop.edu) Attendance Required for Synchronous Online Discussion Section (Enrollment is approximately 12 students per section) The discussion sections will meet ONLINE as follows: Mon 10:00 am to 10:50 am 2

3 Mon 2:00 pm to 2:50 pm Tues 9:00 am to 9:50 am Tues 1:00 pm to 1:50 pm Wed 11:00 am to 11:50 am Wed 2:00 pm to 2:50 pm Thurs 9:00 am to 9:50 am Thurs 3:00 pm to 3:50pm Fri 11:00 am to 11:50 am Fri 1:00 pm to 1:50 pm Required Readings Evaluation Criteria Assigned primary articles and review articles from the current scientific literature. Readings can be downloaded from the Canvas course website. It is strongly suggested that reading materials are printed in color to view experimental data. There will also be demos and supplemental videos that can be accessed through the course website. Breakdown of total grade (1,000 points total): Weekly Participation (Answer questions within videos) (10%) Weekly Discussions (Piazza) (5%) Weekly Homework (5%) Project I-Media Assignment (20%) Project II-Written Assignment (20%) Midterm (20%) Final (20%) Letter Grading A (>92%); A- (90-91%) B+ (86-89%); B (82-85%); B- (80-81%) C+ (76-79%); C (70-75%) D (60-69%); F (<60%) Weekly Activities (required): 1. Watch the all videos assigned each week (Professor s Bio, Mini-Lectures, Tours, Interviews, Demos, Films) 2. Answer questions embedded within the videos 3. Complete assigned homework and submit to your TA (due the day before your discussion section) 4. Attend online discussion section 5. Participate in weekly Case Study blog for your discussion section on Piazza (new case each week) Midterm Week 6 The final will be administered at your campus testing facility and will cover material from weeks 1 to 5. Media Assignment due Week 8 Your assignment is to make a project about DMD in a video format. It could be music video that contains relevant lyrics, or narrated activity (demonstration, game, exhibition, interview) with a person that has or had experience or connection to Duchenne Muscular Dystrophy. Individual that could be included are DMD patient itself, or cousin, friend, physician, nurse, physical therapist, or any other social worker that had experiences contacting patients with DMD). See details of assignment instructions below (page 5 of Syllabus). 3

4 Written Assignment due Week 10 Your assignment is to write the paper in which you would provide an evaluation of a data analysis approach of a primary research paper from the subjects related to DMD that made the most impact on your personal learning. (For detailed instructions see page 9 of the Syllabus.) Final during Finals Week The final will be administered at your campus testing facility and will cover material from weeks 6 to 10. Class Policies: The midterms and final will be closed book. There are no make-up midterms or quizzes. If you feel that a clerical error or oversight was made in the grading of your midterm/quiz, please submit your request with a cover letter detailing a written explanation within 5 calendar days to the TA. II. Expectations and Learning Goals/Outcomes Student Responsibility for Learning: (What do we expect of you?): Tune into lectures regularly and watch them in a timely manner Attend your assigned discussion section and be ready to actively engage in the class Turn in your own original work that reflects your time, effort, and understanding Use the resources available to you, both through the university and online, to ensure that your skills are at the levels they need to be for college level work Assess your own progress often and respond promptly to address any deficiencies or weaknesses Accept the consequences when you do not meet your responsibilities as a student Faculty Responsibility for Teaching: (What do we expect of me?) As responsible instructors, all lecturers will: Be clear about what you are expected to learn Provide real world examples and provide insight on subjects Bring in resources and tools from the real world into the class No surprises, no tricks! Make learning fun Use the Canvas course website for calendar and grading Answer questions in a patient and thoughtful manner Be approachable Pace appropriately and realistically Be a person of character and integrity Speak slowly and clearly Course Learning Objectives: Students who successfully complete this course will be able to: 1. Illustrate mechanisms of skeletal and cardiac muscle contractility 2. Understand complex molecular and cellular mechanisms of disease 3. Design personal medicine approaches aimed at correcting genetic mutations using several different methods 4. Predict outcomes of oligonucleotide induced exon skipping on mrna transcripts 5. Explain and illustrate approaches to gene discovery, including disease-associated genes 6. Evaluate ligand-receptor binding data; design experiments to quantitate protein-protein interactions 7. Understand the biochemical methods to purify large protein complexes composed of peripheral and integral membrane proteins; interpret data from protein purification experiments 8. Critically evaluate current scientific research 9. Create a scientific abstract to reflect findings from experimental research 10. Design experiments to support a hypothesis or to support a scientific conclusion 4

5 11. Design and interpret pre-clinical trials/data from animal models 12. Understand the role of compensatory mechanisms and their potential for therapy 13. Evaluate pre-clinical outcome measures 14. Interpret data from diagnostic molecular, cellular, and physiological assays and evaluate the strengths and weaknesses 15. Explain the role of inflammation in disease pathology 16. Understand the role of satellite cells in muscle regeneration 17. Appreciate the complex social effects of life-threating illnesses on families and communities 18. Evaluate ethical issues pertaining to biomedical research 19. Identify and evaluate the financial conflicts regarding biopharmaceutical research 20. Track and correlate biotech stock prices as they relate to clinical trial data MEDIA PROJECT ASSIGNMENT (detailed instructions) Your assignment is to create a community research project about DMD or other muscular dystrophy in a video format. It could be music video that contains relevant lyrics, or narrated activity (demonstration, game, exhibition, interview) with a person that has experience or connection to Duchenne Muscular Dystrophy or other forms of muscular dystrophy discussed in the course. Individuals that could be included are individuals living with muscular dystrophy or family members, friends, physicians, nurses, physical therapists, caregivers, politicians, advocates, or social workers that have experience with muscular dystrophy. While completing this assignment you agree to adhere to the UCLA Student Conduct Code and will not carry out any illegal or questionable activities. You also agree to not risk harming yourself or others in anyway. If you creating music video, the lyrics should contain technical information about DMD that you have learned in the PS121 lectures or reading materials. Also you should mention your name and your campus in the video (either verbally or in writing)! Your video must be original work, but parodies of your favorite songs are allowed if you plan on making a music video. HOW LONG PROJECT SHOULD BE? The length should be between 2 3 minutes. No vulgarity or nudity keep it PG/PG-13 ; Be respectful; your classmates will be watching this video. You will work in teams of up to 3 students from your campus and all members will receive the same grade for the assignment. HOW TO SUBMIT? Due date: Week 8th Tuesday, at 8am Submission checklist: Check logistics of Video submission with Ava 1. Video Fill out Video Sign-up GoogleDoc (on CANVAS) to submit your video. You will have to include full names, ID#s, and addresses for all teammates. You must also provide an active online link to your video (preferably YouTube). 2. Lyrics include lyrics in your video. This can be done with basic editing software or with YouTube once you have uploaded your video file. Contact your TAs or Ava for more help. *If your video is submitted after this deadline, it will be graded, but you will be deducted 1 point off of your video score (max 20 points if submitted on time) for every 10 minutes of tardiness. GRADING? Dr. Crosbie-Watson and the TAs will evaluate the videos and assign points (0, 5, or 10, 15 or 20 points). Students will also anonymously evaluate their peers. The evaluations will be aggregated and the top 10 videos will receive 20 points. *The top 10 videos will receive 20 points. 5

6 WEEKLY SCHEDULE à WEEK 0: INTRODUCTION TO COURSE 1. WATCH VIDEO LESSON: How to Navigate the Course & Scientific Teaching Using mechanisms and therapies of disease to teach advanced, critical thinking skills. Discussion of evidencedbased teaching pedagogy based on research by Carl Wieman, Ph.D. (Nobel Laureate), Scientific Teaching by Jo Handelsman, and numerous other scientists. Presentation of Bloom s taxonomy, creating a classroom culture that values inclusion, grading rubrics, summative and formative assessments. We will also discuss required weekly activities, assignments, the midterm, and the final. 2. WATCH PROF BIO: Rachelle Crosbie-Watson, Ph.D. Professor UCLA, Dept. Integrative Biology & Physiology; Dept. of Neurology UCLA Center for Duchenne Muscular Dystrophy 3. WATCH DOCUMENTARY FILM: Darius Goes West This documentary is about a young man, Darius Weems, with DMD who travels across America with his crew in an old van so that Darius can fulfill his wish to touch the Pacific Ocean. Darius is an African American young man raised by a single mother. The film reveals personal, emotional, and economic struggles of coping with a life-threatening illness. Darius watched his older brother die from the same disease. We will also learn what it means to be disabled in America as Darius struggles with many issues such as accessibility and how a person s socioeconomic status can affect the quality of health care. 4. WATCH DOCUMENTARY FILM: Dusty s Trail: Summit of Borneo This documentary is about a young man, Dusty Brandom, and his family roots in Indonesia. We learn about the economic challenges of DMD and how advocates can collectively change policies that affect clinical trails and new treatments. In the film, students have an opportunity to visit third world countries and realize how low standards of care for the poor have adverse outcomes on disease progression, leaving young boys in a prematurely debilitated state. The disparity in health care in lower socioeconomic countries is evaluated. 5. READ THE BOOK INTENSIVE CARE: A FAMILY LOVE STORY by Mary-Lou Weisman. This book is written by the mother of a young boy with DMD and reveals the struggles that all families face when a child has a terminal disorder. 6. READ THE COMMENTARY DISABILITY IS NOT A DISQUALIFICATION By Jesse Shanahan; SCIENCE Vol. 351, Issue 6271, p418, Jan. 22 nd, à WEEK 1: MUSCLE PHYSIOLOGY & DMD CLINICAL PRESENTATION 1. WATCH VIDEO LESSON: Muscle Physiology Specializations of the membrane systems for excitation-contraction coupling. Review muscle fiber structure, excitation-contraction coupling, thin and thick filament structure, cross-bridge cycle, electron microscopy of skeletal muscle, neuromuscular junction structure, membrane structures in muscle that are key to regulating voltage transmission and calcium release. PROF: Professor Rachelle Crosbie-Watson, Ph.D. 2. WATCH LAB TOUR: Determination of Muscle Mechanics using an Isolated Frog Muscle 3. WATCH VIDEO LESSON: DMD Clinical Presentation Description of natural history of DMD, muscle weakness progress, current standards of care. Over the last 4 decades there has been a changing in natural history in Duchenne Muscular Dystrophy affecting both survival and loss of clinically meaningful functions. Specific changes in 6MWT predict worsening and loss of ambulation. Age at loss of ambulation predict later milestones and disease progression. Standards of care and improved respiratory and cardiac management have led to improvements in survival and outcome. 6

7 4. WATCH PROF BIO: Perry Shieh M.D., Ph.D., Professor & Director of the Neuromuscular Medicine Training Program, UCLA, Dept. Neurology 5. WATCH CLINICAL TOUR: Tour of the UCLA Neuromuscular Clinic. Watch a narrated video tour of Dr. Nelson and Dr. Shieh interacting with families living with DMD. à WEEK 2: PATHOLOGY AND GENETICS OF DMD 1. WATCH VIDEO LESSON: Pathology of DMD A Pathologist s View of Muscle: What Muscle Histology Can Tell Us About Muscle Diseases, Pathology, and Cell Biology. Muscle regeneration and degeneration, nuclear localization in muscle cells during health and disease, role of satellite cells in regeneration, myofiber size in development and disease, histological analysis of muscle biopsy sections from normal controls and Duchenne patients and other muscle disorders, using histology as a diagnostic tool, how to correctly process muscle tissue for analysis. 2. WATCH PROF BIO: Négar Khanlou, M.D. Professor, UCLA, Dept. Pathology and Laboratory Medicine 3. WATCH VIDEO LESSON: Genetics of DMD Discovering the Dystrophin Gene Today Compared to 1986: the Revolution in Molecular Genetics. Discovery of dystrophin as the disease gene that causes DMD by Dr. Louis Kunkel, how Turner s syndrome lead to discovery of dystrophin, dystrophin gene structure, dystrophin promoters and tissue specific expression, chromosome walking as methodology to discover dystrophin gene, molecular diagnosis methods (then and now), modern approaches to dystrophin mutation analysis: exome sequencing. 4. WATCH PROF BIO: Stanley Nelson M.D. Professor & Vice-Chair UCLA, Dept. Human Genetics; Dept. Psychiatry Co-Director, UCLA Center for Duchenne Muscular Dystrophy (CDMD) à WEEK 3: DYSTROPHIN-GLYCOPROTEIN COMPLEX & DMD ANIMAL MODELS 1. WATCH VIDEO LESSON: Dystrophin-Glycoprotein Complex Discovery of the purification of the dystrophin-associated glycoprotein complex (DGC), swga lectin chromatography and sucrose gradient centrifugation, identification of sarcoglycans and dystroglycan genes, function of the DGC in membrane stability (evidence presented), how to design and interpret protein purification schemes, how loss of dystrophin protein from the sarcolemma affects expression of the DGC, dystrophin protein structure and protein binding regions, laminin and actin binding properties of the DGC, distinction of G-actin and F-actin, F-actin polymerization kinetics, analysis of dystrophin and F-actin binding, analysis of laminin and alpha-dystroglycan binding. PROF: Professor Rachelle Crosbie-Watson, Ph.D. 3. WATCH. VIDEO LESSON: DMD Animal Models Preclinical Models of DMD. Introduction to mouse models of DMD, naturally occurring mouse models of DMD: mdx mouse, genetically engineered mouse models of DMD, genotypic vs. phenotypic mouse models of DMD, outcome measures for preclinical models that include molecular, histological, and physiological assessments (grip strength, muscle force properties, central nucleation, serum creatine kinase assays, Evans blue dye assays, etc). PROF: Professor Rachelle Crosbie-Watson, Ph.D. 4. WATCH INTERVIEWS WITH DR. CAMPBELL AND DR. ERVASTI 7

8 Dr. Crosbie-Watson interviews scientists Professor and Chair Kevin P. Campbell, Ph.D. (HHMI, University of Iowa College of Medicine and Professor and Chair James Ervasti (University of Minnesota, Minneapolis) on their discovery of the dystrophin-glycoprotein complex. à WEEK 4: EXON SKIPPING THERAPY AND GENE THERAPY 1. WATCH VIDEO LESSON: Exon Skipping Therapy Can Personalized Medicine Correct the Primary Genetic DMD Defect? Leveraging the Muscle Cell s RNA Splicing Machinery to Induce Exon Skipping Introduction of Becker muscular dystrophy (BMD) as an experiment of nature, in-frame versus out-of-frame mutations, introduction to mechanism of exon skipping approach, limitations of exon skipping therapies as a treatment for DMD (efficiency, treatment costs, broad applicability), research approaches to address limitations of exon skipping therapies, how to design anti-sense oligonucleotides (AON) to target specific exons, clinical trail data (Serepta/GSK) and effects on the stock market. 2. WATCH PROF BIO: M. Carrie Miceli, Ph.D. Professor UCLA, Department of Molecular Biology, Immunology, and Molecular Genetics Co-Director, UCLA Center for Duchenne Muscular Dystrophy (CDMD) 3. WATCH VIDEO LESSON: Gene Therapy A major area of focus involves the development of vectors to deliver dystrophin or other genes to muscle for gene therapy. These vectors are being tested for safety and for their ability to halt and/or reverse the dystrophic phenotype. The primary vector being studied is derived from adeno-associated virus (AAV), which efficiently transfers genes to skeletal muscle and heart. Methods are being developed for whole body systemic delivery, and a human clinical trial is being planned. 4. WATCH PROF BIO: Jeffrey Chamberlain, Ph.D. Professor, McCaw Endowed Chair in Muscular Dystrophy Director, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center University of Washington, Seattle Dept. Neurology; Dept. Biochemistry à WEEK 5: COMPENSATORY PATHWAYS 1. WATCH VIDEO LESSON: Compensatory Pathways Introduction of the neuromuscular junction structure, introduction to utrophin, role of utrophin in muscle development, utrophin expression at the neuromuscular junction in normal muscle, utrophin protein binding domains and comparison to dystrophin, increase in utrophin around the extrasynaptic sarcolemma in DMD, original work from Dr. Kay Davies and Dr. Josh Sanes demonstrating the compensatory role of utrophin in mdx mice, demonstration that introduction of utrophin ameliorates DMD in mice. Introduction of α7β1 integrin as another compensatory laminin-binding complex. Discussion of experiments using recombinant laminin in mdx muscle. PROF: Professor Rachelle H. Crosbie-Watson, Ph.D. 2. WATCH VIDEO LESSON: Regulators of Muscle Mass Regulation of muscle mass: myostatin, case study: myostatin treatment ameliorates muscular dystrophy in many animal models, myostatin mutations in cattle, canines, and humans; loss of myostatin improves mdx mouse pathology, myostatin inhibition with antibodies to myostatin, role of myostatin in growth regulation and signaling pathways. PROF: Professor Rachelle H. Crosbie-Watson, Ph.D. 8

9 à WEEK 6: NOS REGULATES BLOOD FLOW & IS A TARGET FOR DMD TREATMENT à MIDTERM THIS WEEK. COVERS WEEK 1 TO 5 MATERIALS 1. WATCH VIDEO LESSON: Clinical Trials Ethical considerations for how to conduct human trials to advance human health. Considerations such as gender, enrollment, outcome measures and conflicts of interest will be discussed using contemporary issues. In her lecture, Dr. Laurie Shaker-Irwin discusses several cases of minority group exploitation in clinical trials. The examples of how younger subjects and cognitively/decisional-impaired subjects may not be able to evaluate all of the benefits and consequences of participating in a clinical trial study are discussed. Further, those lacking sufficient scientific and/or health literacy may not know what their rights are as a subject of a human study. Minority and those without sufficient income may have no choice but to participate in a study. The Tuskegee Syphilis Experiment is discussed. This clinical study was conducted between 1932 and 1972 by the U.S. Public Health Service studying the natural progression of untreated syphilis in rural African-American men in Alabama under the auspices of receiving free health care from the United States government. 2. WATCH PROF BIO: Laurie Shaker-Irwin, Ph.D. Assistant Professor, UCLA, Dept. of Medicine and Clinical and Translational Science Institute (CTSI) 3. WATCH INTERVIEW WITH JENN McNARY AND DR. CARRIE MICELI Dr. Miceli and Jenn McNary both have sons living with DMD. In this interview, they discuss the many struggles of obtaining quality care for their sons as well as the financial toll caused by the large costs of disability. They discuss the role of the FDA and families in advancing clinical trials in DMD. 4. WATCH. VIDEO LESSON: Targeting Blood Flow as a Treatment for DMD Rationale for use of PDE inhibitors in the treatment to restore functional sympatholysis, rationale for testing tadalafil in BMD and DMD, experimental design to measure blood flow during exercise in humans, how to select patients for clinical trial, recruitment of patients, data from short-term treatment, outcomes and future studies: role of Pfizer in current clinical trials. 5. WATCH PROF BIO: Ron Victor, M.D. Professor, UCLA Department of Medicine Director, Cedars-Sinai Hypertension Center of Excellence Associate Director, Cedars-Sinai Heart Institute à WEEK 7: STEM CELL THERAPY & INFLAMMATION IN DMD 1. WATCH VIDEO LESSON: Stem Cell Therapy Definition and properties of muscle stem cells, role of stem cells in self-renewal and muscle regeneration exhaustion of stem cells in DMD, approaches to isolate stem cells, treatment of mouse models of muscular dystrophy with stem cells. 2. WATCH PROF BIO: April Pyle, Ph.D. Associate Professor, UCLA, Dept. Microbiology, Immunology, and Molecular Genetics 3. WATCH VIDEO LESSON: Inflammation in DMD Role of macrophages in dystrophic muscle, how inflammation and fibrosis are connected: a common therapeutic target? What signals inflammation in muscle? Detection of inflammatory cells in muscle and clinical approaches to decrease inflammation. Steroids and their effect on inflammation. 4. WATCH PROF BIO: Melissa J. Spencer, Ph.D. Professor, UCLA, Dept. of Neurology Co-Director, UCLA Center for Duchenne Muscular Dystrophy (CDMD) à WEEK 8: CARDIOMYOPATHY & BIOMECHANICS 9

10 à VIDEO ASSIGNMENTS DUE 1. WATCH VIDEO LESSON: Cardiomyopathy in DMD Cardiomyopathy in DMD: from molecular mechanisms to physiology to treatment approaches. Introduction to cardiac imaging techniques used in the clinic, cardiac and pulmonary function in normal and stressed states, role of calcium regulation in function, congestive heart failure and drug interventions aimed at signaling pathways. 2. WATCH PROF BIO: Andrew D. Watson, M.D., Ph.D. Associate Professor, UCLA Dept. of Medicine 3. WATCH VIDEO LESSON: Biomechanics Biomechanical analysis of gait in individuals with DMD: results from clinical trials physical therapy tools for DMD, clinical outcome assessments for DMD (gait analysis, 6-min walk test), choice and rationale of steroid treatment, discussion for global assessment tool in clinical trails, the role of parent education in disease management and treatment. Dr. Fowler also presents two case studies of families coping with DMD, which reveals the added struggles that minorities with low socioeconomic status encounter when seeking help for their sons with DMD. Physiological outcome measures from each DMD boy are provided as an example of how these factors can negatively impact disease progression. 4. WATCH PROF BIO: Eileen Fowler, Ph.D. Associate Professor, UCLA, Dept. Orthopaedic Surgery à WEEK 9: DYSTROGLYCANOPATHIES 1. WATCH VIDEO LESSON: Dystroglycanopathies-Clinical Presentation Dystroglycanopathies are a clinically heterogeneous group of muscular dystrophies that result from abnormality of alpha-dystroglycan. Forms of dystroglycanopathy will be presented, along with clinical presentations of symptoms and an overview of primary causes of disease. 2. WATCH PROF BIO: Katherine Mathews, M.D. Professor & Director, Division of Neurology and Developmental and Behavioral Pediatrics, University of Iowa College of Medicine, Dept. Pediatrics à WEEK 10: IMPORTANCE OF SUGAR IN MUSCULAR DYSTROPHY à WRITTEN ASSIGNMENTS DUE 1. WATCH VIDEO LESSON: Dystroglyanopathies-Molecular Mechanisms Glycobiology and laminin-binding impact disease. Identification of disease genes with glycosyl transferase functions that target alpha-dystroglycan and affect laminin-binding properties, introduction to WWS, LGMD, CMD, MEB, glycobiology of dystroglycan (including a review of basic glycan structure), role of POMTn1, POMTn2, and other glycosyl transferases. 2. WATCH PROF BIO: Linda Baum, M.D., Ph.D. Professor & Associate Dean, UCLA, Dept. of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine 10