High School Student Internship: Bioinformatics Research and Big Data Analytics for Young Scholars Fall 2023
Instructor:
Drs. Jorge Ortiz,
Naoru Koizumi (nkoizumi@gmu.edu)
Meng-Hao Li (mli11@gmu.edu)
Project 1. Evaluation of Antithymocyte globulin (ATG) + Basiliximab (Simulect) as Induction Therapy in Kidney Transplant Recipients
Background
Transplant recipients take a cocktail of immunosuppressive drugs to reduce the risk of rejection and graft failure. Immunosuppressive therapies are largely classified into two classes. One is known as “induction therapy” and is administered pre-transplant. The other is known as the “maintenance therapy” and is administered post-transplant for life (or until graft failure). Managing immunosuppressive regimen (e.g., which medications to take and how much) has been one of the major remaining challenges that all transplant centers face. These drugs are high in toxicity and increase the risk of infections, while not taking sufficient amount of these drugs would increase the risk of graft failure.
For the induction, there are three major drugs.
- Antithymocyte globulin (“Thymo”)
- Alemtuzumab (“Campath”), and
- Basiliximab (“Simulect”).
For the maintenance, more than 80% uses the combination of:
- Calcineurin inhibitors, which could either be Tacrolimus or Cyclosporine (Many brands e.g., Prograf, Envarsus for Tac and Sandimmune, Gengraf for Cyclosporine, Note: everyone gets this)
- Mycophenolate mofetil (MMF), and
- Steroid (“Prednisone”) (The brands include CellCept, Myfortic, etc., Note: The new trend is to avoid this as much as possible).
This project focuses on the induction therapy (while we control for the maintenance therapy). We will specifically focus on the recent trend that uses “thymo and simulect combination”. This is done by some transplant centers for the patients who cannot take a full doe of thymo (2-3 doses /day) for various reasons such as thrombocytopenia, leukopenia, or cytokine release syndrome. Since using Simulect on its own is considered “too weak”, they often combine with thymo and simulect. We will evaluate whether this approach is as effective as other regimens (thymo only, simulect only, and campath only) for preventing infections, graft failures and patient death up to 3 years. Concurrently, we will also evaluate whether steroid use is effective or not.
Project 2. Evaluation of Pancreatic Re-transplantation Outcomes
Background
The individuals who suffer from Type I diabetes have a higher risk for both kidney and pancreas failures. Type 1 diabetes is caused by the autoimmune destruction of insulin-producing beta cells in the pancreas. Failure to produce insulin, in turn, increases the blood sugar level, which could damage small blood vessels in the kidneys. This condition is known as diabetic nephropathy. For this reason, these patients whose kidneys and pancreas failed due to Type I diabetes tend to go through both kidney and pancreas transplants.
There are three options for those who suffer from kidney and pancreas failures due to Type I diabetes:
- Pancreatic transplants alone (PTA) – while continuing dialysis
- Pancreas after kidney transplants (PAK)
- Simultaneous pancreas kidney transplants (SPK)
Traditionally, SPK is associated with the best outcomes. Prior research shows that the outcomes for kidney retransplants are comparable to primary transplants and are superior to dialysis. In contrast, the data on pancreatic retransplants are derived from small single center reports and these studies have no consensus thus far. Thus, we will analyze this using the transplant national registry data.
Project 3. Evaluation of Transplanting Organs from Drowned Donors
Background
Donor-derived infections, i.e., infections carried by (deceased) organ donors transmitted to organ recipients, are rare but fatal, often involving organ recipient’s death. A recent publication by CDC reported that drowned organ donors can be exposed to environmental molds through the aspiration of water and that transplantation of exposed organs can cause invasive mold infections in recipients.
We will investigate whether the outcomes of drowned donor kidney and liver transplants are worse than the transplants utilizing kidneys and livers from donors who died from other mechanical causes of death. We will compare drowned donor organs to the organs procured from donors who died from 4 most common accidents or injuries, i.e.,
- Drug intoxication
- Gunshot wound
- Blunt injury (may include car accidents), and
- Asphyxiation