Transplant Research and Clinical Trials
Researchers within the Division of Transplantation at the University of Maryland Medical Center are committed to investigating new ways to advance the science of transplantation and ensure better futures for patients in need of transplant or for those who are already living with organ transplants.
The research within the Division of Transplantation falls into several categories:
- Inducing tolerance - teaching the body to accept a foreign graft, such as a transplanted organ, without rejection and with limited or no immunosuppression.
- Immunosuppression medications and medication management - testing the latest medications or combinations of medications to prevent rejection while reducing the "pill burden" on patients and creating protocols that demonstrate long-term success with fewer side effects.
- Increasing the number of available donor organs - through tissue regeneration and systematic sourcing of available organs.
- Advancements in surgical technique - use of new operative tools, materials and techniques, including the single-incision laparoscopic surgery used on living kidney donors.
- Using bone marrow-derived stem cells to decrease rejection - could help eliminate need for immunosuppression in all types of organ recipients.
- Bridge-to-transplant technology - medical devices used to help patients who are in need of transplant but either not at the top of the wait list or without an available donor organ.
Research in Lung Healing
Clinicians and scientists are invested in improving the outcomes of patients with acute and chronic lung diseases. Research is being conducted through the Lung Healing Program, both in laboratory settings and with UMMC patients who could benefit from the latest in lung disease treatment.
Collaborators in the Lung Healing Program include cardiothoracic surgeons, critical care doctors, trauma surgeons, nurses within these specialty areas, and researchers from the University of Maryland School of Medicine.
Learn more about ongoing research within the Lung Healing Program.
Advances in Hepatitis C Treatment
University of Maryland Medical Center (UMMC) is one of the country's premier hospitals treating patients with liver failure. Our doctors and researchers help to discover new medications and treatment options for many liver diseases, including hepatitis C.
Today, the U.S. Food and Drug Administration (FDA) is approving new medications that will treat cirrhosis of the liver faster, easier and more effectively in patients with liver damage caused by chronic hepatitis C.
New Hepatitis C Medications Available from UMMC PhysiciansToggle accordion item
Previously, drugs for hepatitis C were protease inhibitors, which means they attacked a certain part of the hepatitis C virus. In late 2013, a new category of medicines came out, called polymerase inhibitors. These medications attack a different part of the hepatitis C virus.
Polymerase inhibitors are more effective than any other drug so far. Patients experience high cure rates, even when they have cirrhosis of the liver, which has been difficult to treat. We offer these new medications to all patients who have hepatitis C.
This new category of drugs is safe and has limited side effects. They also:
- Do not interact with other drugs as previous medications have
- Have higher cure rates than in the past
- Do not cause rashes, anemia, itching or burning anal pain
- Cause less fatigue than previous medicines for hepatitis C
Liver Transplantation and Hepatitis C AdvancesToggle accordion item
Many transplant surgeons are excited about the new medical treatments for hepatitis C because these medications make both pre- and post-transplant care more effective. They are also leading to better long-term outcomes for patients.
We offer all patients with hepatitis C the opportunity to live free of the virus with the new medications. A dedicated nurse and pharmacist will help patients with issues surrounding insurance coverage of these new drugs.
The advantages of the new medications include:
- Fewer interactions with immunosuppressant medications: Previous hepatitis C drugs had major drug interactions with immunosuppressant medications. These interactions made these medications problematic for patients with a transplant.
- Preventing cirrhosis: Cirrhosis caused by hepatitis C is the No. 1 cause of liver transplant. Medications like ones that have come out in the last few years will help treat patients with hepatitis C earlier in the disease process. This will lower the number of patients who need a liver transplant because of hepatitis C.
- Saving lives after transplantation: For a patient who has hepatitis C, the hepatitis will always come back, even after a liver transplant. However, these new medications can eliminate hepatitis C before transplant. This can prevent the hepatitis virus from destroying the transplanted liver. By eliminating hepatitis C in patients who have cirrhosis before they have a transplant, we do not have to treat hepatitis C after transplant because the virus is already cured. Learn more about liver transplant.
As part of an academic medical center, our Liver Center has participated in several clinical trials involving direct acting antivirals (DAAs).
Contact UsToggle accordion item
To schedule a conversation with the liver team, please call 1-410-328-5941.
For referring physicians: To refer a patient or get more information, please call 1-800-373-4111. A physician service representative from Consultation and Referral Services will direct your call to the appropriate physician or department.
For more details, please visit our section for referring physicians.
Recellularization: The Future of Liver TransplantationToggle accordion item
Patients with heart failure have heart pumps and ventricular assist devices (VADs) that allow their hearts to keep beating. Patients with kidney failure have dialysis to clean the toxins from their blood. Diabetics have insulin to correct the under performance of their pancreas. But there are no options other than transplantation for patients with liver failure, and unfortunately more people are in of need of liver transplants than there are donor organs available.
Dr. John LaMattina, assistant professor and director of the University of Maryland Medical Center’s living donor liver transplant program, is committed to finding new options for patients with end-stage liver disease. His first step was to work with colleagues in the Division of Transplantation to establish the largest adult living donor liver transplant program in the state of Maryland, which enables close friends or relatives to donate part of their liver to their sick loved one after thorough a examination and extensive physical evaluation. This living donor surgery is designed to help transplant patients earlier in their liver failure so that they recover more quickly and do not become sicker while awaiting a deceased donor organ.
In addition to his clinical solutions for maximizing available livers, Dr. LaMattina fosters a passion for basic science research, which culminated during his training years in a fellowship in the Transplant Biology Research Center at Massachusetts General Hospital in Boston where he studied transplant immunology and tolerance of transplanted tissue.
Now with a lab of his own, Dr. LaMattina uses a pre-clinical model to investigate the possibility of stripping native cells from donor livers, leaving only the translucent scaffolding of the liver, and recellularizing them with stem cells from a needy recipient. If perfected, this procedure could eliminate deaths caused by the shortage of livers available for transplantation. The science is complex, but the concept is fairly simple, like gutting the inside of a home and rebuilding the floor plan.
Imagine if patients could become both their own donor and recipient. It would look something like this: patient donates his/her own healthy stem cells. Physician scientists inject stem cells into an empty liver scaffold where cells multiply over a few weeks until they have filled the scaffold and regenerated a full liver. Surgeons would transplant that newly recellularized liver into the donor-recipient.
The risk of rejection would be much lower since the cells came from the recipient's own body. And the wait time to transplant would be weeks instead of months, requiring just a few weeks to harvest stem cells and recellularize a liver scaffold.
Research is in the early stages, but Dr. LaMattina believes he will see significant advancements in the next five to 10 years with increased funding and research support.
Basic, Translational, and Clinical Research and Trials
Actively Funded GrantsToggle accordion item
Department of Defense Grants
Adult Tissue-Derived Stem Cells and Tolerance Induction in Nonhuman Primates for Vascularized Composite Allograft Transplantation
Congressionally Directed Medical Research Programs (CDMRP)
Vascularized Bone Marrow Regulates Alloresponses to Vascularized Composite Allografts
Dept. of Defense – AFIRM II
Upregulation of bone marrow compartment mediated immunomodulation for vascularized composite allografts
Congressionally Directed Medical Research Programs
Restorative Transplantation Research Cooperative Agreement
Prospective observational study of HIV+ deceased donor transplant for HIV+ recipients (ongoing, recruiting)
The primary objective is to evaluation the safety of HIVDD solid organ transplantation to include kidney alone, liver alone, or simultaneous liver/kidney in HIV+ recipients.
The primary outcome is 3 year patient survival.
Randomized controlled trial of Inflixmab (Remicade®) Induction Therapy for Deceased Donor Kidney Transplant Recipients (ongoing, recruiting)
The objective of this study is to determine the efficacy of intravenous infliximab administered at the time of transplantation, prior to reperfusion, on a 2-year kidney transplant survival and function.
Impact of CCR5 Blockade in HIV+ Kidney Transplant Recipients (ongoing, recruiting)
The primary objectives are to evaluate impact of CCR5 blockade (maraviroc, MVC) on renal function at week 52 post-transplant, and the overall safety and tolerability of CCR5 blockade in the HIV+ kidney transplant recipient.
Basic Science Research
Induction and Migration of Regulatory T Cells: Role of Lymphotoxin.
The major goals of this project are: 1.) Determine if LT regulation of Treg afferent lymphatic migration is required for suppression of Tconv in tissues and dLN; and 2.) Determine how Treg LTab - LEC LTbR interactions regulate migration.
Lymph Node Structure and Function in Tolerance: Role of Laminins
The major goals of this project are: 1.) Determine the role of CR laminins in transplant tolerance; 2) Determine how laminins regulate HEV and CR entry of T cells and their conversion to iTreg in tolerance; and 3.) Determine how laminins regulate the migration and fate of a later cohort of naive T cells that newly enter the HEV and CR tolerant environment.
Bromberg (Co-PI and mentor for C. Colin Brinkman and Wenji Piao)
Living Legacy Foundation Transplantation Grant
The role of lymphotoxin in Treg migration and suppressor function
The major goals of this project are: 1.) If Treg migrate from blood to tissues, but cannot migrate out of tissues, does this change suppression of nonTreg in the tissues? 2.) What is the fate of non-migrated Treg and are they suppressive? and 3.) If Treg cannot migrate out of tissues, does this change suppression of nonTreg cells in the dLN?
Living Legacy Foundation Transplantation Grant
Microbiota Structure and Transplant Outcomes: Preclinical Studies
The major goals of this project are: 1.) Determine the effects of different microbiota on allograft survival and alloimmunity; 2.) Determine how the microbiota population structure evolves during allograft survival and rejection; and 3.) Determine how transplantation, immunosuppression and antibiotics alter microbiota structure
National Multiple Sclerosis Society
Harnessing intra-lymph node controlled release to promote myelin-specific tolerance.
The major goals of this project are: 1.) Test if depots promote TREGS and stop or reverse progressive autoimmune disease (EAE); 2.) Decipher the local and systemic changes in myelin response that lead to tolerance; and 3.) Test if depots can stop or reverse relapsing-remitting autoimmune disease (RR-EAE).
VA Maryland Health Care System
Tunable Assembly of Regulatory Immune Signals to Promote Myelin-specific Tolerance
The major goals of this project are: 1.) Characterize iPEM material properties and screen in primary mouse cells and MS patient samples; 2.) Assess potency in progressive autoimmune disease (EAE) and test if tolerance is myelin-specific; 3.) Elucidate the structural and functional changes in LNs, spleen, and the CNS that lead to tolerance; and 4.) Test if tolerance is generalizable to other self-antigens using relapsing-remitting model (RR-EAE).
Engineering local lymph node function to promote systemic, antigen-specific tolerance in T1D.
The major goals of this project are: 1.) Design and screen depots loaded with Rapa and T1D antigens in dendritic cell (DC) and transgenic T cell culture; 2.) Test depot efficacy in T1D mouse models during early or late stage treatment and determine the specificity of tolerance; and 3.) Elucidate the structural and functional changes in LNs, spleen, and pancreatic islets that lead to tolerance.
UMD-UMB 2017 Research and Innovation Seed Grant
Local engineering of the lymph node microenvironment in non-human primates to support translational therapies targeting autoimmunity and transplant rejection.
The goal of the present study is to demonstrate the potency of intra-lymph node (iLN) injection of microparticle (MPs) depots loaded with antigens and the immunosuppressive drugs rapamycin (Rapa) in non-human primates (NHP). Aim 1: Test the tolerogenic potential of iLN-MP to prevent responses to model antigens in NHPs. Aim 2: Assess skin graft survival and donor-specific hypo-responsiveness promoted by iLN-MPs
Harnessing biomaterials to study the link between local lymph node function and systemic tolerance.
The major goals of the project are: 1.) Determine how local signals in LNs polarize T cell function and program systemic tolerance; 2.) Decipher the impact of signal location, delivery route, and kinetics on T cell polarization; 3.) Compare the local structure and function of depot-treated LNs to distal LNs, spleen, and CNS; and 4.) Test if link between local function and systemic tolerance is generalizable to other self-antigens.
Clinical Science Research
Bromberg (site PI)
NIAID U01 AI063594
CTOT-19- Randomized Controlled Trial of Infliximab (Remicade®) Induction Therapy
For Deceased Donor Kidney Transplant Recipients
The objective of the study is to determine the efficacy of intravenous infliximab administered at the time of transplantation, prior to reperfusion, on 2-year kidney transplant survival and function.
Bromberg (site PI)
Innate B Cell Immunity and Antibody-Mediated Rejection of Human Kidney Allografts
The goal of the present study is to further investigate the role of Nabs IgG in the outcome of kidney transplants in a large group of patients treated at multiple centers. Our main objective is to assess the value of serum IgG Nabs as a biomarker for rejection (ABMR) and ultimately graft loss following kidney transplantation. We will also examine whether the development of IgG Nabs correlate with anti-HLA antibodies and DSA.
1 U01 DK116095-01
U Maryland Mid-Atlantic APOLLO Research Network Omic and Clinical Center
The major goals of this project are to investigate the following hypotheses:
- Functional APOL1 risk alleles in AA can activate and/or promote pathophysiologic pathways leading to maladaptive responses to renal injury resulting in increased susceptibility to albuminuria, hypertension, progressive CKD and/or ESRD in kidney donors
- Among allograft recipients, kidney specific APOL1 risk alleles can activate and/or promote pathophysiologic pathways leading to maladaptive responses to renal injury and increased risk of albuminuria, progressive CKD and/or renal allograft failure
- APOL1 risk alleles can activate and/or promote pathophysiologic pathways leading to increased blood pressure and cardiovascular (CV) events in renal allograft donors and recipients.
Drugs Currently in Phase 2 or 3 TestingToggle accordion item
Reduce the Severity of DGF in Recipients of a Deceased Donor Kidney (currently recruiting)
A Multicenter, Prospective, Double-Blind, Randomized, Placebo-Controlled, Phase 3 Study of BB3 to Reduce the Severity of Delayed Graft Function in Recipients of a Deceased Donor Kidney
QPI-1002 for Prevention of Delayed Graft Function in Recipients of an Older Donor Kidney Transplant (ReGIFT) (ongoing, not recruiting)
A Phase 3, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of QPI-1002 for Prevention of Delayed Graft Function in Recipients of a Donation After Brain Death Older Donor Kidney Transplant
PKD Clinical and Translational Core Study (ongoing, currently recruiting)
The Baltimore Polycystic Kidney Disease Clinical and Translational Core Study
Letermovir (MK-8228) Versus Placebo in the Prevention of Clinically-Significant Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients (MK-8228-001)
A Phase 3, Randomized, Double-Blind, Active Comparator-Controlled Study to Evaluate the Efficacy and Safety of MK-8228 (Letermovir) Versus Valganciclovir for the Prevention of Human Cytomegalovirus (CMV) Disease in Adult Kidney Transplant (ongoing, recruiting)
The primary objective is to evaluate the efficacy of letermovir (LET) versus valganciclovir (VGCV), as measured by the proportion of participants with adjudicated CMV disease through 52 weeks post-transplant.
Normothermic Liver Preservation
A Multicenter, Randomized, Controlled Trial to Compare the Efficacy of Ex-Vivo Normothermic Machine Perfusion with Static Cold Storage in Human Liver Transplantation (ongoing, recruiting)
The objective of this study is to compare the effect of NMP to SCS in preventing preservation-related graft injury.
Study to Assess the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de Novo Kidney Transplant Recipients
A Phase 2a, Randomized, Open-Label, Active Control, Multi-Center Study to Access the Efficacy and Safety of Bleselumab in Preventing the Recurrence of Focal Segmental Glomerulosclerosis in de novo Kidney Transplant Recipients (ongoing, recruiting).
To assess the efficacy of the bleselumab regimen (basiliximab induction, tacrolimus, steroids and bleselumab) compared with the Standard of Care (SOC) regimen (basiliximab induction, tacrolimus, steroids and mycophenolate mofetil [MMF]) in the prevention of the recurrence of focal segmental glomerulosclerosis (rFSGS) defined as nephrotic range proteinuria with protein-creatinine ratio (>- 3.0g/g) through 3 months post-transplant. Death, graft loss or lost to follow-up will be imputed as rFSGS.
Cellular Immunotherapy in Recipients of HLA-matched, Living Donor Kidney Transplants
A Phase 3 Prospective, Randomized, Multi-Center, Open-Label, Controlled Trial to Assess the Efficacy and Safety of Cellular Immunotherapy with MDR-101 for Induction of Immune Tolerance in Recipients of HLA-matched, Living Donor Kidney Transplants (not yet started, not recruiting)
To evaluate achievement of induction of functional immune tolerance by cellular immunotherapy with MDR-101 in recipients of human leukocyte antigen (HLA)-matched, living donor kidney transplants.
Studies Currently in Phase 4 TestingToggle accordion item
To Compare the Effects of Immediate-release Tacrolimus and Astagraf XL on Donor-Specific Antibody (DSA) Formation and the Development of Immune Activation (IA) in de Novo Kidney Transplant Recipients (ASTOUND) (ongoing, not recruiting)
Astagraf XL® to Understand the Impact of Immunosuppression on De Novo DSA Development and Chronic Immune Activation in Kidney Transplantation
Studies to Devise New Tests to Reduce RejectionToggle accordion item
Non Invasive Blood Test to Diagnose Acute Rejection AFTER Kidney Transplantation (DART) (ongoing, not recruiting)
Circulating Donor-Derived Cell-free DNA in Blood for Diagnosing Acute Rejection in Kidney Transplant Recipients