MSTPublications: August 2025

 

headshot of MSTP student Atlee Witt
Atlee Witt

Changes in functional connectivity in relapsing-remitting multiple sclerosis spinal cord measured via region-based and data-driven analyses.

Witt AA, Combes AJE, Sengupta A, Zhang X, Stubblefield S, McKnight CD, McGonigle T, McGrath M, Stewart I, Sweeney G, Prock LE, Houston D, Vandekar S, O’Grady KP, Rogers B, Gore J, Smith SA.
Imaging Neurosci (Camb). 2025 Jun 20;3:IMAG.a.51. doi: 10.1162/IMAG.a.51. eCollection 2025.
PMID: 40800997 Free PMC article.

Abstract
The clinical picture of persons with multiple sclerosis (pwMS), a neuroinflammatory disease characterized by demyelination, does not consistently correlate with pathology noted on clinical magnetic resonance imaging (MRI). Functional MRI (fMRI) is a valuable tool to understand neural network alterations resulting from structural damage, with studies in the brain employing both region-of-interest and data-driven assessment of functional connectivity. However, similar studies in the spinal cord (SC) remain limited given the challenge of imaging a small structure in an area with substantial physiologic noise. We sought to apply resting-state fMRI at 3T in the SC of healthy controls (HC) and persons with relapsing-remitting MS (pwRRMS) to assess differences in functional connectivity and relate functional markers to clinicial measures of disability. Consistent with prior SC studies, we determined strongest functional connectivity between ventral gray matter horns in both HCs and pwMS and diminished mobility associated with reduced functional connectivity. Using independent-component analysis, we observed a possible compensatory mechanism of increased connectivity in earlier compared with later stages of relapsing-remitting MS. Further exploration is warranted, and our findings support the notion of functional alterations in the SC of pwMS.
Keywords: functional magnetic resonance imaging; independent component analysis; magnetic resonance imaging; multiple sclerosis; spinal cord.

 

headshot of MSTP studnet Reilly Fankhauser
Reilly Fankhauser

Tumor Lysis Syndrome with Venetoclax/ Carfilzomib/ Dexamethasone for Relapsed/Refractory Multiple Myeloma: A Case Report.
Fankhauser R, Lu A, Kassim A, Biltibo E.
Reports (MDPI). 2024 Nov 29;7(4):108. doi: 10.3390/reports7040108.
PMID: 40757710 Free PMC article.

Abstract
Background and Clinical Significance: Tumor lysis syndrome (TLS) is a rare occurrence in patients treated with venetoclax mono- or combination therapy, and clear protocols guiding TLS prophylaxis are lacking. Case Presentation: We present a 53-year-old male with a history of relapsed refractory multiple myeloma (RRMM) with t(11;14) treated with venetoclax, carfilzomib and dexamethasone (VenKd), resulting in TLS with subsequent renal failure. Repeat marrow biopsy showed no monoclonal plasma cells but extensive fibrosis. Venetoclax was reintroduced after two months with marrow recovery. Venetoclax was titrated from 200 to 400 mg daily alongside IV fluids and allopurinol without TLS recurrence. Conclusions: Here, we highlight the importance of risk stratification, dose titration, and TLS prophylaxis with venetoclax use in RRMM.
Keywords: 14); BCL-2; carfilzomib; dexamethasone; relapsed refractory multiple myeloma (RRMM); t(11; tumor lysis syndrome (TLS); venetoclax.

 

headshot of MSTP student Pershad Yash
Yash Pershad

Closing the loop: Teaching single-cell foundation models to learn from perturbations.

Pershad Y, Nandi TN, Van Amburg JC, Parker AC, Ostrowski L, Giannini HK, Ong D, Heimlich JB, Obeng EA, Ericson K, Agarwal A, Madduri RK, Bick AG.
bioRxiv [Preprint]. 2025 Jul 12:2025.07.08.663754. doi: 10.1101/2025.07.08.663754.
PMID: 40672312 Free PMC article. Preprint.

Abstract
The application of transfer learning models to large scale single-cell datasets has enabled the development of single-cell foundation models (scFMs) that can predict cellular responses to perturbations in silico. Although these predictions can be experimentally tested, current scFMs are unable to “close the loop” and learn from these experiments to create better predictions. Here, we introduce a “closed-loop” framework that extends the scFM by incorporating perturbation data during model fine-tuning. Our closed-loop model improves prediction accuracy, increasing positive predictive value in the setting of T-cell activation three-fold. We applied this model to RUNX1-familial platelet disorder, a rare pediatric blood disorder and identified two therapeutic targets (mTOR and CD74-MIF signaling axis) and two novel pathways (protein kinase C and phosphoinositide 3-kinase). This work establishes that iterative incorporation of experimental data to foundation models enhances biological predictions, representing a crucial step toward realizing the promise of “virtual cell” models for biomedical discovery.

 

headshot of MSTP student Peggy Randon
Peggy Randon

Spatial Proteomics Redefines Psoriasis as a Vertically Stratified, Immunometabolic Tissue State.
Randon PM, Ward NL.
J Invest Dermatol. 2025 Jul 31:S0022-202X(25)02249-3. doi: 10.1016/j.jid.2025.06.1584. Online ahead of print.
PMID: 40742347 No abstract available.

 

 

 

 

 

headshot of MSTP student Seth Reasoner
Seth Reasoner

The urinary microbiome: the next frontier of bacterial ecology.
Reasoner SA, Francis J, Hadjifrangiskou M.
J Bacteriol. 2025 Jul 24:e0010525. doi: 10.1128/jb.00105-25. Online ahead of print.
PMID: 40704791 Free article. Review.

Abstract
The human urinary tract, once presumed to be sterile, has emerged as a new frontier of microbial ecology. Recent advancements in high-throughput sequencing technologies have revealed the complexity and diversity of microbial communities that reside within the urinary tract. This mini-review discusses the prominent bacteria identified in the urinary microbiome and their correlations with various urologic conditions. This review serves to summarize the current state of urobiome research and chart a path for ongoing discovery. Additionally, we address the methodological challenges in urinary microbiome research, emphasizing the need for standardization in study protocols and the refinement of bioinformatics tools. We highlight that although differences in urobiome composition have been described for various urologic diseases. Similarly, the pathophysiologic source and consequences of those differences remain uncertain. We outline the steps to move urobiome research from descriptive to mechanistic studies, emphasizing rigorous study design, integrating multi-omics approaches, and developing robust model systems for experimental investigation. Finally, we outline critical questions for future investigation aimed at elucidating the intricate connections between the urinary microbiome and host health.
Keywords: microbiome; urinary microbiome; urinary tract; urobiome.

White matter microstructure and macrostructure brain charts across the human lifespan.
Kim ME, Gao C, Ramadass K, Newlin NR, Kanakaraj P, Bogdanov S, Rudravaram G, Archer D, Hohman TJ, Jefferson AL, Morgan VL, Roche A, Englot DJ, Resnick SM, Beason Held LL, Cutting L, Barquero LA, D’archangel MA, Nguyen TQ, Humphreys KL, Niu Y, Vinci-Booher S, Cascio CJ; HABS-HD Study Team; Alzheimer’s Disease Neuroimaging Initiative; BIOCARD Study Team; Li Z, Vandekar SN, Zhang P, Gore JC, Landman BA, Schilling KG.
bioRxiv [Preprint]. 2025 May 9:2025.05.08.652953. doi: 10.1101/2025.05.08.652953.
PMID: 40654938 Free PMC article. Preprint.

TRANSFORMER-BASED T1-TRACTOGRAPHY.
Yoon J, Rao M, McMaster EM, Cho C, Newlin NR, Schilling KG, Landman BA, Moyer D.
Proc IEEE Int Symp Biomed Imaging. 2025;2025:10.1109/isbi60581.2025.10981144. doi: 10.1109/isbi60581.2025.10981144. Epub 2025 May 12.
PMID: 40814567

Multimodal state-dependent connectivity analysis of arousal and autonomic centers in the brainstem and basal forebrain.
Pourmotabbed H, Martin CG, Goodale SE, Doss DJ, Wang S, Bayrak RG, Kang H, Morgan VL, Englot DJ, Chang C.
Imaging Neurosci (Camb). 2025 Jul 21;3:IMAG.a.91. doi: 10.1162/IMAG.a.91. eCollection 2025.
PMID: 40800913 Free PMC article.

Transformer patient embedding using electronic health records enables patient stratification and progression analysis.
Xian S, Grabowska ME, Kullo IJ, Luo Y, Smoller JW, Walunas TL, Wei WQ, Jarvik GP, Mooney SD, Crosslin DR.
NPJ Digit Med. 2025 Aug 14;8(1):521. doi: 10.1038/s41746-025-01872-z.
PMID: 40813607 Free PMC article.

2-Hydroxybenzylamine for Treatment of Atrial Fibrillation: A First-in-Human Clinical Pilot Trial.
Yoneda ZT, O’Neill M, Crawford DM, Ao M, Sun L, El-Harasis M, Pitchford LM, Rathmacher JA, Montgomery J, Shen S, Estrada JC, Saavedra P, Ellis CR, Richardson T, Kangasundram A, Crossley G, Akers WS, Ye F, Roden DM, Michaud GF, Shoemaker MB.
Circ Arrhythm Electrophysiol. 2025 Jul 25:e013378. doi: 10.1161/CIRCEP.124.013378. Online ahead of print.
PMID: 40709466

Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.
Rosales A, Blondel LO, Hull J, Gao Q, Aykun N, Peek JL, Vargas A, Fergione S, Song M, Wilson MH, Barbas AS, Asokan A.
Nat Biomed Eng. 2025 Jul;9(7):1086-1100. doi: 10.1038/s41551-024-01341-0. Epub 2025 Feb 5.
PMID: 39910375 Free PMC article.

Partial correction of cystinuria type A in mice via kidney-targeted transposon delivery.
Woodard LE, Welch RC, Menshikh A, Luo W, Williams FM, Peek JL, Sha F, Veach RA, Kaja A, Beckerman TM, Ikizler TA, Wilson MH.
Mol Ther Nucleic Acids. 2025 Jul 21;36(3):102639. doi: 10.1016/j.omtn.2025.102639. eCollection 2025 Sep 9.
PMID: 40791872 Free PMC article.

Evolution of clonal hematopoiesis on and off lenalidomide maintenance for multiple myeloma.
Cooperrider JH, Karaoglu DA, Kubicki T, Jiang CR, Postich E, Shimamoto K, Arnold O, Macaraeg J, Ramsland A, Pula A, Kishtagari A, Pershad Y, Mack TM, Jones A, Bick AG, Savona M, Drazer MW, Dytfeld D, Jakubowiak A, Derman BA, Saygin C.
Leukemia. 2025 Jul 16. doi: 10.1038/s41375-025-02707-2. Online ahead of print.
PMID: 40670674 No abstract available.

Germline genetic variation impacts clonal hematopoiesis landscape and progression to malignancy.
Liu J, Tran D, Xue L, Wiley BJ, Vlasschaert C, Watson CJ, MacGregor HAJ, Zong X, Chan ICC, Das I, Uddin MM, Niroula A, Griffin G, Ebert BL, Mack T, Pershad Y, Sharber B, Berger M, Zehir A, Ptashkin R, Levine RL, Papaemmanuil E, Joseph V, Gao T, Kemel Y, Mandelker D, Stopsack KH, Pharoah PDP, Mukherjee S, Ding L, Cao Y, Walter MJ, Blundell JR, Chatterjee N, Offit K, Godley LA, Link DC, Stadler ZK, Bick AG, Natarajan P, Bolton KL.
Nat Genet. 2025 Aug;57(8):1872-1880. doi: 10.1038/s41588-025-02250-x. Epub 2025 Jul 15.
PMID: 40664769 Free PMC article.

Successful extracorporeal membrane oxygenation bridge to lung transplant with a patient transported from Hawaii to Nashville, Tennessee.
Adjei E, Gannon WD, Petree BS, Stokes JW, Demarest CT, Petrovic M, Wang C, Rice TW, Erasmus D, Trindade AJ, Bacchetta M, Hoetzenecker K.
JTCVS Tech. 2025 May 23;32:219-224. doi: 10.1016/j.xjtc.2025.05.002. eCollection 2025 Aug.
PMID: 40814650 Free PMC article. No abstract available.

 10-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.
Williams AM, Ahmad A, Trahanas J, Bommareddi S, Absi T, Quintana E, Wang CC, Petrovic M, McGann K, Devries S, Lowman J, Siddiqi H, Amancherla K, Brinkley M, Menachem JN, Pedrotty D, Punnoose L, Rali AS, Sacks S, Zalawadiya S, Bacchetta M, Schlendorf K, Shah AS, Lima B.
J Heart Lung Transplant. 2025 Jul 21:S1053-2498(25)02121-7. doi: 10.1016/j.healun.2025.07.015. Online ahead of print.
PMID: 40701206

PGI2 restricts trained ILC2 responses in allergic inflammation.
Zhou W, Zhang J, Norlander AE, Cook DP, Toki S, Abney M, Rusznak M, Thomas C, Warren C, Richmond BW, Gibson-Corley K, Milne GL, Newcomb DC, Peebles RS Jr.
J Immunol. 2025 Jul 1;214(7):1582-1591. doi: 10.1093/jimmun/vkaf088.
PMID: 40334085