MSTPublications: April 2024
Solid organ transplant recipients exhibit more TET2-mutant clonal hematopoiesis of indeterminate potential not driven by increased transplantation risk.
Silver AJ, Vlasschaert C, Mack T, Sharber B, Xu Y, Bick AG, Pinson CW, Savona MR.
Clin Cancer Res. 2024 Mar 29. doi: 10.1158/1078-0432.CCR-23-3840. Online ahead of print.
Purpose: Solid organ transplant recipients comprise a unique population of immunosuppressed patients with increased risk of malignancy, including hematologic neoplasms. Clonal hematopoiesis of indeterminate potential (CHIP) represents a known risk factor for hematologic malignancy and this study describes the prevalence and patterns of CHIP mutations across several types of solid organ transplants.
Experimental design: We use two national biobank cohorts comprised of >650,000 participants with linked genomic and longitudinal phenotypic data to describe the features of CHIP across 2,610 individuals who received kidney, liver, heart, or lung allografts.
Results: We find individuals with an allograft prior to their biobank enrollment had an increased prevalence of TET2 mutations (OR 1.90; p = 4.0e-4), but individuals who received transplants post-enrollment had a CHIP mutation spectrum similar to that of the general population, without enrichment of TET2. Additionally, we do not observe an association between CHIP and risk of incident transplantation among the overall population (HR 1.02; p = 0.91). And in an exploratory analysis, we do not find evidence for a strong association between CHIP and rates of transplant complications such as rejection or graft failure.
Conclusions: These results demonstrate that recipients of solid organ transplants display a unique pattern of clonal hematopoiesis with enrichment of TET2 driver mutations, the causes of which remain unclear and are deserving of further study.
Brain-derived neurotrophic factor scales presynaptic calcium transients to modulate excitatory neurotransmission.
Wang CS, McCarthy CI, Guzikowski NJ, Kavalali ET, Monteggia LM.
Proc Natl Acad Sci U S A. 2024 Apr 23;121(17):e2303664121. doi: 10.1073/pnas.2303664121. Epub 2024 Apr 15.
Brain-derived neurotrophic factor (BDNF) plays a critical role in synaptic physiology, as well as mechanisms underlying various neuropsychiatric diseases and their treatment. Despite its clear physiological role and disease relevance, BDNF’s function at the presynaptic terminal, a fundamental unit of neurotransmission, remains poorly understood. In this study, we evaluated single synapse dynamics using optical imaging techniques in hippocampal cell cultures. We find that exogenous BDNF selectively increases evoked excitatory neurotransmission without affecting spontaneous neurotransmission. However, acutely blocking endogenous BDNF has no effect on evoked or spontaneous release, demonstrating that different approaches to studying BDNF may yield different results. When we suppressed BDNF-Tropomyosin receptor kinase B (TrkB) activity chronically over a period of days to weeks using a mouse line enabling conditional knockout of TrkB, we found that evoked glutamate release was significantly decreased while spontaneous release remained unchanged. Moreover, chronic blockade of BDNF-TrkB activity selectively downscales evoked calcium transients without affecting spontaneous calcium events. Via pharmacological blockade by voltage-gated calcium channel (VGCC) selective blockers, we found that the changes in evoked calcium transients are mediated by the P/Q subtype of VGCCs. These results suggest that BDNF-TrkB activity increases presynaptic VGCC activity to selectively increase evoked glutamate release.
Atlee Witt (G1) published a small article on research and mentorship in the Radiological Society of North America’s “Med Student Pulse” in which Atlee shares advice from her PI and MSTP classmates.
Deep conditional generative model for longitudinal single-slice abdominal computed tomography harmonization.
Yu X, Yang Q, Tang Y, Gao R, Bao S, Cai LY, Lee HH, Huo Y, Moore AZ, Ferrucci L, Landman BA.
J Med Imaging (Bellingham). 2024 Mar;11(2):024008. doi: 10.1117/1.JMI.11.2.024008. Epub 2024 Apr 2.
Large language models facilitate the generation of electronic health record phenotyping algorithms.
Yan C, Ong HH, Grabowska ME, Krantz MS, Su WC, Dickson AL, Peterson JF, Feng Q, Roden DM, Stein CM, Kerchberger VE, Malin BA, Wei WQ.
J Am Med Inform Assoc. 2024 Apr 13:ocae072. doi: 10.1093/jamia/ocae072. Online ahead of print.
Who Can Be Discharged Home after Adult Spinal Deformity Surgery?
Jonzzon S, Chanbour H, Johnson GW, Chen JW, Metcalf T, Lyons AT, Younus I, Liles C, Abtahi AM, Stephens BF, Zuckerman SL.
J Clin Med. 2024 Feb 27;13(5):1340. doi: 10.3390/jcm13051340.
The insula: Leveraging cellular and systems-level research to better understand its roles in health and schizophrenia.
Kittleson AR, Woodward ND, Heckers S, Sheffield JM.
Neurosci Biobehav Rev. 2024 May;160:105643. doi: 10.1016/j.neubiorev.2024.105643. Epub 2024 Mar 24.
Impact of inpatient addiction psychiatry consultation on opioid use disorder outcomes.
Kast KA, Le TDV, Stewart LS, Wiese AD, Reddy IA, Smith J, Marcovitz DE, Reese TJ.
Am J Addict. 2024 Mar 28. doi: 10.1111/ajad.13540. Online ahead of print.
Lung CT harmonization of paired reconstruction kernel images using generative adversarial networks.
Krishnan AR, Xu K, Li TZ, Remedios LW, Sandler KL, Maldonado F, Landman BA.
Med Phys. 2024 Mar 26. doi: 10.1002/mp.17028. Online ahead of print.
An in vitro CRISPR screen of cell-free DNA identifies apoptosis as the primary mediator of cell-free DNA release.
Davidson BA, Miranda AX, Reed SC, Bergman RE, Kemp JDJ, Reddy AP, Pantone MV, Fox EK, Dorand RD, Hurley PJ, Croessmann S, Park BH.
Commun Biol. 2024 Apr 10;7(1):441. doi: 10.1038/s42003-024-06129-1.
FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.
Liu Y, Reed SC, Lo C, Choudhury AD, Parsons HA, Stover DG, Ha G, Gydush G, Rhoades J, Rotem D, Freeman S, Katz DW, Bandaru R, Zheng H, Fu H, Adalsteinsson VA, Kellis M.
Nat Commun. 2024 Mar 30;15(1):2790. doi: 10.1038/s41467-024-47196-6.
Clonal Hematopoiesis and Inflammation in the VasculaturE (CHIVE): a prospective, longitudinal cohort and biorepository.
Shannon ML, Heimlich JB, Olson S, Debevec A, Copeland Z, Kishtagari A, Vlasschaert C, Snider CA, Silver AJ, Brown D, Spaulding TP, Bhatta MR, Pugh K, Stockton SS, Ulloa J, Xu Y, Baljevic M, Moslehi J, Jahangir E, Ferrell PB Jr, Slosky DA MD, Bick AG, Savona MR.
Blood Adv. 2024 Apr 12:bloodadvances.2023011510. doi: 10.1182/bloodadvances.2023011510. Online ahead of print.
Cost-Effective and Scalable Clonal Hematopoiesis Assay Provides Insight into Clonal Dynamics.
Mack T, Vlasschaert C, von Beck K, Silver AJ, Heimlich JB, Poisner H, Condon HR, Ulloa J, Sochacki AL, Spaulding TP, Kishtagari A, Bejan CA, Xu Y, Savona MR, Jones A, Bick AG.
J Mol Diagn. 2024 Apr 6:S1525-1578(24)00076-X. doi: 10.1016/j.jmoldx.2024.03.007. Online ahead of print.
Ablation of IFNγ in myeloid cells suppresses liver inflammation and fibrogenesis in mice with hepatic small heterodimer partner (SHP) deletion.
Zhu L, Litts B, Wang Y, Rein JA, Atzrodt CL, Chinnarasu S, An J, Thorson AS, Xu Y, Stafford JM.
Mol Metab. 2024 Apr 6;83:101932. doi: 10.1016/j.molmet.2024.101932. Online ahead of print.
VHL loss reprograms the immune landscape to promote an inflammatory myeloid microenvironment in renal tumorigenesis.
Wolf MM, Madden MZ, Arner EN, Bader JE, Ye X, Vlach L, Tigue ML, Landis MD, Jonker PB, Hatem Z, Steiner KK, Gaines DK, Reinfeld BI, Hathaway ES, Xin F, Tantawy MN, Haake SM, Jonasch E, Muir A, Weiss VL, Beckermann KE, Rathmell WK, Rathmell JC.
J Clin Invest. 2024 Apr 15;134(8):e173934. doi: 10.1172/JCI173934.