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      <h1>Cellular and Molecular Therapeutics</h1>
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            <div class="field field--name-field-component-lab-banner-descr field--type-text-long field--label-hidden field__item"><p>The Cellular and Molecular Therapeutics Laboratory, led by Dr. John F. Tisdale, is working on multiple strategies both in the laboratory and in the clinic to cure sickle cell disease by repairing or replacing the precursor bone marrow cells that give rise to sickled red blood cells.<br />
In addition, strategies to correct the underlying mutation which causes sickle cell disease are being pursued utilizing newly developed gene editing tools, and work in the laboratory to develop methods for efficient editing of hematopoietic stem cells is underway.</p>
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<img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="John Tisdale" data-src="/sites/default/files/styles/square_image/public/2017-12/John%20Tisdale%27s%20picture%2011.2010.jpg?itok=eGPV23bT" class="b-lazy image-style-square-image" />


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<span>John Tisdale, M.D.</span>

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            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Senior Investigator and Director</div>
      
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              <div class="field__item"><p>Sickle cell disease (SCD) has its roots in genetic mutations that cause a single amino acid change in the β-globin chain of hemoglobin A and thereby confer protection against malaria. Whereas one copy of the mutated gene is an asset in areas where malaria is endemic, two copies become a liability regardless of geographic location. The unadulterated mutation encourages hemoglobin to clump and deform red blood cells, leading to anemia, increased hemolysis, and vascular occlusions that affect multiple organs. Dr. Tisdale is working on multiple strategies both in the laboratory and in the clinic to cure sickle cell disease by repairing or replacing the precursor bone marrow cells that give rise to sickled red blood cells.</p>

<p>Bone marrow transplants from healthy donors are used successfully to treat certain blood cancers for which the course of the disease is so severe that the destruction of the patient’s own immune system through high-dose chemotherapy and radiation seems an effective compromise. However, the therapeutic balance in the case of SCD is less clear; children tolerate transplants more successfully, but they are also less imminently threatened by the disease. The success of conventional transplants in adults, whose need is more immediate, is less clear.</p>

<p>The issue of immune tolerance is, of course, central to transplantation research. Dr. Tisdale has an active research program in trying to characterize tolerance and create conditions in which patients will more easily tolerate donor cells and tissues without the need for destroying the immune system or perpetual use of immunosuppressant drugs.</p>

<p>Dr. Tisdale and his colleagues recently completed a modified bone marrow transplant strategy for the first time in adult patients with sickle cell disease. In a recent study, they demonstrated that they could transplant bone marrow cells from HLA-matched sibling donors without needing to completely destroy the patient’s immune system. This “mixed chimerism” appears to persist without the need for the ongoing immunosuppression that other types of transplants require. The important innovation in the protocol was the short-term destruction of the patient’s T-lymphocytes through a depleting antibody, followed by their regrowth under the influence of the mTOR inhibitor rapamycin. The next phase of this work is to extend the concept with alternative strategies to include donors who are not perfectly matched (thereby including a half-matched sibling, parent, or child).</p>

<p>Dr. Tisdale and his colleagues also have an ongoing research agenda to find a gene therapy strategy for SCD. After extracting and isolating precursor CD34+ cells from patients, they use viral transduction to insert a correct copy of the β-globin gene before returning the cells to the patient’s bone marrow. The laboratory has focused on optimizing the conditions for viral transduction, including selecting and modifying viral strains for study in animal models, optimizing growth conditions for transduced hematopoietic cells, and designing gene vectors to ensure appropriate placement and expression of the inserted gene.</p>

<p>Finally, strategies to correct the underlying mutation which causes SCD are being pursued utilizing newly developed gene editing tools, and work in the laboratory to develop methods for efficient editing of hematopoietic stem cells is underway.</p>
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<span>Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People with Higher Risk of Transplant Failure</span>

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												Do you or your child have sickle cell disease and have a stem cell donor? This study is exploring how to improve bone marrow transplant procedures so the body better accepts donor stem cells. Participants in this study must be at least 4 years old. This study is located in Bethesda, Maryland.
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<span>Collection and Storage of Umbilical Cord Stem Cells for Treatment of Sickle Cell Disease</span>

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												Are you pregnant and willing to donate umbilical cord blood to support future sickle cell disease therapies? This study seeks to determine the best way to collect, store, and handle blood from newborns to help researchers improve future sickle cell disease therapies. To participate in this study, you must be pregnant, 45 years old or younger, and willing to donate umbilical cord blood from your newborn. Newborns may be healthy or at risk for sickle cell disease or sickle cell trait. This study is located in Bethesda, Maryland.
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<span>Addition of JSP191 (C-kit Antibody) to Nonmyeloablative Hematopoietic Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia</span>

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													Are you or your child at least 13 years old and have sickle cell disease?
												In this stidy, researchers are trying to find out if a new medication improves the success of a blood stem cell transplant. People 13 years old or older who are eligible for a blood stem cell transplant to treat sickle cell disease may be able to participate. Healthy family members over age 13 who are matched to transplant recipients are also needed to donate blood for the study. This study is taking place at the National Institutes of Health Clinical Center in Bethesda, Maryland.
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               <span>Authors: </span>Leonard A, Tisdale J, Abraham A.
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                2020 Feb 07</span>:
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               <span>Authors: </span>Murad MH, Liem RI, Lang ES, Akl EA, Meerpojl JJ, DeBaun MR, Tisdale JF, Brandow AM, Lanzkron SM, Chou ST, Webb S, Mustafa RA
            </div>
                                                                                                                        
            <span>
            Blood Adv
      
                2019 Dec 10</span>;3(23):3945-50
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                                                    <a href="https://www.ncbi.nlm.nih.gov/pubmed/31794603" aria-label="2019 sickle cell disease guidelines by the American Society of Hematology: methodology, challenges, and innovations." class="read-publications">Read Publication</a>
                            
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               <span>Authors: </span>Raines LN, Hsieh MM, Nassehi T, Drysdale CM, Tisdale JF, Uchida N
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            <span>
            Cytotherapy
      
                2019 Dec 01</span>;21(12):1206-15
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                                                    <a href="https://pubmed.ncbi.nlm.nih.gov/31784240/" aria-label="Ex vivo immunological evaluation of stable mixed chimeric patients after matched related donor allogeneic transplantation in sickle cell disease." class="read-publications">Read Publication</a>
                            
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               <span>Authors: </span>Metais JY, Doerfler PA, Mayurananthan T, Bauer DE, Fowler SC, Hsieh MM, Katta V, Keriwala S, Lazzarotto CR, Luk K, Neel MD, Perry SS, Peters ST, Porter SN, Ryu BY, Sharma A, Shea D, Tisdale JF, Uchida N, Walfe SA, Woodward KJ, Wu Y, Yao Y, Zeng J
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            <span>
            Blood Adv
      
                2019 Nov 12</span>;3(21):3379-92
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            <div class="publicationAuthors">
               <span>Authors: </span>Alexis Leonard, Morgan Yapundich, Tina Nassehi, Jackson Gamer, Claire M Drysdale, Juan J Haro-Mora, Selami Demirci, Matthew M Hsieh, Naoya Uchida, John F Tisdale 
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            <span>
            Mol Ther Methods Clin Dev
      
                2019 Nov 11</span>;15:430-437
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                                                    <a href="https://pubmed.ncbi.nlm.nih.gov/31890735/" aria-label="Low-Dose Busulfan Reduces Human CD34 + Cell Doses Required for Engraftment in C-Kit Mutant Immunodeficient Mice." class="read-publications">Read Publication</a>
                            
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                    John Tisdale, M.D.
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            <div class="clearfix text-formatted field field--name-field-person-bio field--type-text-with-summary field--label-hidden field__item"><p>John Tisdale graduated from the College of Charleston in South Carolina with a B.A. in chemistry in 1986. He then earned his M.D. from the Medical University of South Carolina in 1990. He did his internship and residency at Vanderbilt University School of Medicine and was Chief Resident at the Nashville Veterans Administration Medical Center from 1993 to 1994. He joined the NHLBI in 1994, where he has been a hematology fellow, senior staff fellow, and Clinical Investigator. He joined the Molecular and Clinical Hematology Branch of the National Institute of Diabetes and Digestive and Kidney Diseases in 1998 as a tenure track Investigator and was tenured in 2007. In 2011 the College of Charleston recognized Dr. Tisdale with the Alumni of the Year Award and the Pre-Medical Society’s Outstanding Service Award in Medicine. He was recently elected to the American Society for Clinical Investigation and is a member of the American Society of Hematology. Dr. Tisdale has authored or coauthored more than 140 papers.</p>
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<span>Wynona Coles, RRT</span>

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<span>Selami Demirci, Ph.D.</span>

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<span>Bjorg Gudmundsdottir, MBA, Ph.D.</span>

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<span>Juan Haro-Mora, Ph.D.</span>

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<span>Stephanie Helwing </span>

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<span>Matthew Hsieh, M.D.</span>

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<span>Alexis Leonard, M.D.</span>

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            <h4>
            
<span>Oswald Phang </span>

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<span>Tiffani Farrey </span>

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            <h4>
            
<span>Naoya Uchida, M.D., Ph.D.</span>

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            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Staff Scientist</div>
      
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<img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Jessica Peterson" data-src="/sites/default/files/styles/square_image/public/2021-09/Jessica_Peterson.jpg?itok=OWSEYlWI" class="b-lazy image-style-square-image" />


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            <h4>
            
<span>Jessica Peterson </span>

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            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Supervisory Staff Assistant</div>
      
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</div>
      
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            <h4>
            
<span>Morgan Yapundich </span>

        </h4>
        

    <div class="node__content">
        
            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Postbaccalaureate Fellow</div>
      
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<img loading="lazy" src="/modules/custom/nhlbi_blazy/images/clear.png" width="200" height="200" alt="Rick Gustason" data-src="/sites/default/files/styles/square_image/public/2020-01/Rick.jpg?itok=G6zcldlk" class="b-lazy image-style-square-image" />


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            <h4>
            
<span>Rick Gustafson </span>

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            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Research Nurse</div>
      
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            <h4>
            
<span>Robert  Donahue </span>

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            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Collaborative Investigator</div>
      
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</div>
      
            </div>
    
            <h4>
            
<span>Claire  Drysdale </span>

        </h4>
        

    <div class="node__content">
        
            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Postbaccalaureate Fellow</div>
      
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            <h4>
            
<span>Khaled Essawi </span>

        </h4>
        

    <div class="node__content">
        
            <div class="field field--name-field-employment-title field--type-string field--label-hidden field__item">Predoctoral Fellow</div>
      
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