The effect of HIV and drugs of abuse on the blood-brain barrier
Name:
Dr. Allison Andrews
Email
andrews.allison@ufl.edu
Phone
(352) 294-5275
Faculty Department/Division
Pathology Immunology and Laboratory Medicine
This project is primarily:
Basic
Research Project Description:
Despite the use of Anti-retroviral therapy, rates of HIV-associated neurocognitive disorders (HAND) remain high in people living with HIV. A hallmark of HAND is blood-brain barrier disruption and inflammation in the CNS. Additionally, people with HIV commonly use drugs of abuse, which is known to impact HIV neuropathogenesis and contribute to neurocognitive disorders (NCI). The goal of this work is to examine the effect of various drugs of abuse on the blood-brain barrier, HIV replication and inflammation in the central nervous system (CNS).
Does this project have an international component or travel?
No
Multimodal AI for High‑Resolution Detection of Coronary Artery Fibrosis in Routine H&E Sections
Name:
Dr. Shyam Gajavelli
Email
gajavelli.s@ufl.edu
Phone
(786) 493-2178
Faculty Department/Division
Pathology Immunology and Laboratory Medicine
This project is primarily:
Basic
Research Project Description:
Title: Multimodal AI for High Resolution Detection of Coronary Artery Fibrosis in Routine H&E Sections
2026 Summer MSRP Pathology Project Proposal
Background
Dramatic progress has been made in cardiac transplantation with 1-year survival increasing at 22% in 1969 to greater than 90% by 2019[1, 2]. Procurement of hearts from circulatory death donors (DCD) with thoracoabdominal normothermic regional perfusion (TA-NRP) has been on the rise[3-5]. No statistically significant differences in 12-month survival were found between the orthotopic heart transplant (OHT) groups receiving hearts from donors after brain death (DBD) or DCD in a systematic review and meta-analysis of 10 studies with outcomes and methods of donation[6]. Recent analysis of all DCD heart transplants recorded in the United Network for Organ Sharing (UNOS) database between January 2019 and April 2025, reported encouraging: 1-year survival exceeded 90%. Among 1682 transplants with complete data, ex vivo heart perfusion (EVHP) was used in 1175 cases, while 507 hearts were transplanted without it. There is growing acceptance of hearts from donors with prolonged agonal times (> 30 min) in the United States —more than 140 such transplants were performed in 2024, just a fraction of the donor pool. Spline modeling showed rising mortality beginning ∼20 min of AP for static-preserved grafts, with a flat risk curve under EVHP. Static-preserved prolonged-AP grafts had higher odds of acute rejection before discharge (aOR 2.56; 95% CI 1.07-6.14; p = 0.04)[7]. With follow-up extended to 3 years post-transplant, significant differences emerged in subsequent years with a difference of 4.7% (p = 0.007) in year 2; 5.3% (p = 0.025) in year 3[8]. However, the primary graft dysfunction (PGD), an early, acute form of heart failure occurring within the first 24 hours to days after transplantation due to severe ventricular dysfunction was higher in DCD (17%) compared with DBD (8%) patients[9]. Although PGD is not associated with mortality at 24- (HR 0.72, p = 0.442) and 72-h (HR 0.74, p = 0.457)[6], in some cases DCD recipients were likely to experience severe biventricular PGD than DBD recipients (19% vs 7.4%; P = 0.004)[10] which could be both jeopardize patient outcome and increase cost of care[11]. The relationship between donor and recipient age does not significantly affect survival following heart transplant, older donor hearts (age ≥50 years) achieved comparable perioperative outcomes and long-term graft survival after careful selection. However, higher rates of cardiac allograft vasculopathy (CAV) that do not affect long-term graft survival need further investigation [12, 13].
A 10-minute asystole during NRP i.e., asystolic warm ischemic time (AWIT) predicts mortality and PGD severity and other recipient outcomes in TA-NRP-recovered DCD hearts. Efforts to minimize AWIT are crucial to optimize postoperative outcomes[14]. Pulseless electrical activity (PEA) WIT (PWIT) greater than 12 minutes is significantly associated with increased mortality and severe PGD in TA-NRP-recovered DCD hearts. Retrospective analysis of TA-NRP cohort supported the hypothesis that maintaining low intraoperative oxygen debt summarized by oxygen extraction ratio (O₂ER) via goal-directed perfusion (GDP) modifies arterial WIT and early outcomes in DCD OHT. The GDP was measured from minute-by-minute cardiopulmonary bypass (CPB) records, low O₂ER i.e., >20% was dichotomized at the cohort mean (≤70 vs >70 minutes), patients were stratified by AWIT (<10 vs ≥10 minutes). The prolonged-AWIT/high-O₂ER group (n=18) had the highest incidence of severe PGD (22%), 30-day mortality (17%), and 90-day mortality (22%). Within prolonged-AWIT recipients, lower O₂ER burden (≤70 minutes) was associated with reduced odds of severe PGD (OR 0.09, 95% CI 0.07-0.87) and the composite endpoint (OR 0.13, 95% CI 0.07-0.54). Continuous modeling demonstrated consistent directional associations between increasing O₂ER burden and adverse outcomes[15].
Recently, Dr. Amancherla’s group analyzed endomyocardial biopsy (EMB) tissues from 62 children and adult OHT patients (<4%DCD) with spatial transcriptomics campaign and reported existence of distinct transcriptomic profiles associated with resolution or rejection. The report identified 216 genes across 6 cell types along, IL6-JAK-STAT3, IFNα/IFNγ response, and TNFα signaling, cell-specific gene expression signatures (cell states e.g., SPP1 macrophage numbers) associated with cell-mediated rejection and CAV development[16]. CAV is consistently accompanied by immune infiltrates surrounding affected coronary arteries, including antibody-producing plasma cells (PC). The exclusive presence of anti-bilirubin antibodies suggest local heme catabolism driven bilirubin accumulation creates a prominent target for intragraft antibody responses. Bilirubin-specific antibodies and hemecatabolic pathways may contribute to CAV pathogenesis warrants further investigation[17]. Giga TIME virtual population revealed new spatial and combinatorial protein activation patterns that were not visible to a human observer [18, 19].
Hypothesis
Taken together access to coronary arterial HE stained slides of de-identified patients but correlated with outcomes (e.g., UF CaRe-T1D biobank) could test if multimodal AI can extract PGD/CAV features (patterns/correlations e.g., CD68 and CD138 co-occurrence with fibrosis) that are invisible (not a pattern) to human pathologist. Examination of endomyocardial biopsy (EMB) H&E slides with multimodal AI (CD68, CD138 proximity signature) in collaboration with Intelligent Clinical Care Center (IC3) (https://ic3.center.ufl.edu/), could identify features associated with PGD and CAV.
Role of medical student
The student will need to find dozens of parameter values in the literature, understand how to create ordinary differential equation (ODE) models of immune dynamics, and learn how to run mathematical analysis on a model in MATLAB[20]. As the work could take at least 6 months to year, the work could be continued by a group of volunteers until it reaches a fundable project status. The medical student could revisit the project during breaks and possibly use it if planning to pursue The Artificial Intelligence in Biomedical and Health Sciences (AIBHS) or aid preparation for a residency in Cardiac transplantation.
Funding
None
Relevant publications
Hosenpud JD, Bennett LE, Keck BM, Fiol B, Boucek MM, Novick RJ: The Registry of the International Society for Heart and Lung Transplantation: sixteenth official report–1999. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 1999, 18(7):611-626.
Kwon JH, Ghannam AD, Shorbaji K, Welch B, Hashmi ZA, Tedford RJ, Kilic A: Early Outcomes of Heart Transplantation Using Donation After Circulatory Death Donors in the United States. Circ Heart Fail 2022, 15(12):e009844.
Williams AM, Ahmad A, Bommareddi S, Lima B, Pasrija C, Nguyen D, Petrovic M, Wang CC, Quintana E, Siddiqi HK et al: Two hundred cases of cardiac donation after circulatory death utilizing normothermic regional perfusion: The 4-year Vanderbilt experience. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2025, 44(11):1703-1711.
Williams AM, Ahmad A, McGann K, Wang CC, Bommareddi S, Lima B, Petrovic M, Quintana E, Absi T, DeVries SA et al: Reanimation-less rapid recovery of a donor heart after circulatory death with prolonged 8-hour ischemic time. The Journal of Heart and Lung Transplantation.
Goodwin ML, Nickel IC, Li H, Kagawa H, Kyriakopoulos CP, Hanff TC, Stehlik J, Drakos SG, Selzman CH: Direct procurement with machine perfusion and normothermic regional perfusion in donation after circulatory death heart transplantation. J Thorac Cardiovasc Surg 2025, 170(1):256-265.e256.
Kwon YIC, Keller M, Elhigzi K, Adibi I, Jones HC, Lai A, Park AM, Tchoukina IF, Shah KB, Fitch Z et al: Early Outcomes of Primary Graft Dysfunction Comparing Donation After Circulatory and Brain Death Heart Transplantation: An Analysis of the UNOS Registry. Clin Transplant 2025, 39(7):e70222.
Berg AR, Krishnan A, Heng EE, Choi AY, Garrison AC, Alnasir DI, Chawannuch R, Shudo Y, Joseph Woo Y, MacArthur JW: Ex-vivo heart perfusion attenuates early post-transplant risk after prolonged agonal period in DCD heart transplantation. The Journal of Heart and Lung Transplantation 2026, 45(3):337-346.
Nguyen A, Rana A, Shafii A, Loor G, Civitello A, Reyes JEM, Frazier OH, Rosengart T, Liao K: Potential intermediate-term survival differences among heart transplant recipients from circulatory death vs brain death donors. JHLT open 2025, 9.
Jolliffe J, Brookes J, Williams M, Walker E, Jansz P, Watson A, MacDonald P, Smith J, Bennetts J, Boffini M et al: Donation after circulatory death transplantation: a systematic review and meta-analysis of outcomes and methods of donation. Annals of cardiothoracic surgery 2025, 14(1):11-27.
Ayer A, Truby LK, Schroder JN, Casalinova S, Green CL, Bishawi MA, Bryner BS, Milano CA, Patel CB, Devore AD: Improved Outcomes in Severe Primary Graft Dysfunction After Heart Transplantation Following Donation After Circulatory Death Compared With Donation After Brain Death. Journal of cardiac failure 2023, 29(1):67-75.
Cho PD, Kim ST, Zappacosta H, White JP, McKay S, Biniwale R, Ardehali A: Severe primary graft dysfunction in heart transplant recipients using donor hearts after circulatory death: United States experience. The Journal of Heart and Lung Transplantation 2025, 44(5):760-769.
Jawitz OK, Raman V, Klapper J, Hartwig M, Patel CB, Milano C: Donor and recipient age matching in heart transplantation: analysis of the UNOS Registry. Transplant international : official journal of the European Society for Organ Transplantation 2019, 32(11):1194-1202.
Li SS, Makarem A, Funamoto M, Michel E, Kreso A, Rabi AS, Ton V-K, Zlotoff D, Yang BQ, Lewis G et al: Outcomes of donation after brain death heart transplantation from older donors: A contemporary analysis of the UNOS database. JHLT open 2025, 9.
Williams AM, Ahmad A, Trahanas J, Bommareddi S, Absi T, Quintana E, Wang CC, Petrovic M, McGann K, Devries S et al: Ten-minute asystolic warm ischemic time (AWIT) predicts mortality and severe primary graft dysfunction in donation after circulatory death hearts recovered with thoracoabdominal normothermic regional perfusion. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2025.
Williams AM, Ahmad A, Trahanas J, Bommareddi S, McGann KC, Wang CC, Petrovic M, Absi T, Quintana E, DeVries S et al: Intraoperative Oxygen Debt is Associated with Early Clinical Outcomes After Prolonged Asystolic Warm Ischemia Time in Donation After Circulatory Death Heart Transplantation. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 2026.
Amancherla K, Taravella Oill AM, Bledsoe X, Williams AL, Chow N, Zhao S, Sheng Q, Bearl DW, Hoffman RD, Menachem JN et al: Dynamic responses to rejection in the transplanted human heart revealed through spatial transcriptomics. bioRxiv 2025:2025.2002.2028.640852.
See SB, Aguiar T, Dietzel M, Ausmeier M, Nguyen HT, Mashiko S, Donadeu L, Cordero H, Roy P, Roson L et al: Dominant intragraft plasma cells targeting bilirubin implicate local heme catabolism in human cardiac allograft vasculopathy. J Clin Invest 2026, 136(3).
Valanarasu JMJ, Xu H, Usuyama N, Kim C, Wong C, Argaw P, Ben Shimol R, Crabtree A, Matlock K, Bartlett AQ et al: Multimodal AI generates virtual population for tumor microenvironment modeling. Cell 2026, 189(2):386-400.e319.
Wu E, Bieniosek M, Wu Z, Thakkar N, Charville GW, Makky A, Schürch CM, Huyghe JR, Peters U, Li CI et al: ROSIE: AI generation of multiplex immunofluorescence staining from histopathology images. Nature communications 2025, 16(1):7633.
Ingalls BP: Mathematical Modeling in Systems Biology: An Introduction: MIT Press; 2022.
Does this project have an international component or travel?
No