About

Kevin Lin is a faculty member in the Program in Applied Mathematics at the University of Arizona. His research interests include applied mathematics, specifically nonlinear dynamics, computational methods, nonequilibrium statistical physics, and mathematical biology. He is involved in various research groups related to applied mathematics, biomathematics, computational neuroscience, data assimilation, nonlinear dynamics, physics, statistical physics, and uncertainty quantification. His work focuses on advancing understanding and computational techniques within these areas, contributing to the broader field of applied mathematics and its interdisciplinary applications.

Research topics

• Biology
• Genetics
• Internal medicine
• Chemistry
• Medicine
• Cancer research
• Computer Science
• Artificial Intelligence
• Endocrinology
• Biochemistry
• Archaeology
• Oncology
• Geology
• Cell biology
• Bioinformatics
• History
• Computational biology

Selected publications

• SCOPE: Localizing fate-decision states and their regulatory drivers in single-cell differentiation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-09

  articleOpen accessSenior author

  Identifying the precise transcriptomic states at which cells commit to a lineage (branchpoints) and the temporal lag in which chromatin accessibility foreshadows gene expression (epigenetic priming) remain fundamental challenges in developmental biology. While current methods for single-cell sequencing data effectively capture developmental flow, they often lack a principled mechanism for delineating the discrete boundaries, a crucial aspect required to map the molecular logic of lineage commitment. We present SCOPE (Semi-supervised Conformal Prediction), a framework that transforms high-dimensional single-cell measurements into rigorous, discrete prediction sets of all plausible future fates. By formalizing fate uncertainty via conformal inference, SCOPE localizes the precise biological windows during which multipotent progenitors specify their fate. In multi-omic data, SCOPE uncovers epigenetic priming and identifies its driving transcription factors by detecting regimes where chromatin-derived prediction sets resolve toward terminal fates significantly before their transcriptomic counterparts. We apply SCOPE across simulations, lineage-traced mouse hematopoiesis, multiple human hematopoietic datasets, and human retinogenesis to demonstrate its broad applicability and ability to recapitulate known fate specification drivers. Ultimately, SCOPE provides a statistically grounded foundation for localizing fate decisions across biological replicates and modalities, offering a robust tool for identifying the onset of lineage specification in complex developmental systems.

  PublisherOA PDFDOI

• Abstract 4763: Alternative splicing of ABI1 by enzalutamide treatment drives tumor plasticity in prostate cancer

  Cancer Research · 2026-04-03

  article1st authorCorresponding

  Abstract Prostate cancer affects nearly 1.4 million new patients each year and is the second leading cause of cancer-related deaths. While initial stages of disease are driven by androgen receptor (AR) signaling and treatable with androgen-depravation therapies (ADT) and androgen receptor pathway inhibitors (ARPIs), tumors frequently recur with resistance to these therapies. The development of resistance is driven by tumor plasticity in which mutations, epigenetic changes, and alternative splicing generate phenotypic alterations that allow for adaptations to circumvent AR inhibition.Recent studies have shown that treatment with second generation ARPIs such as enzalutamide may be the very driver of the plasticity leading to its resistance. Enzalutamide treatment has been shown to induce global splicing changes, and promote a high-grade, treatment-resistant, neuroendocrine phenotype. One potential link between the changes in RNA-splicing and the development of a neuroendocrine phenotype is Abelson Interactor 1 (ABI1), a multi-isoform scaffolding protein known to be a regulator of prostate cancer progression. In this study, we aimed to identify how ARPI treatment induces isoform-specific changes in ABI1, and how these changes drive prostate cancer progression. Using a combination of cell line, patient-derived and animal models of prostate cancer, we were able to determine that ARPI treatment deregulates inclusion of ABI1-exon 4, which is critical to ABI1’s DNA-binding ability. This dysregulation in turn alters the expression of many genes involved in pathways of transcriptional regulation and stress response during enzalutamide treatment. Taken together, these findings shed new light on the mechanisms behind the development of enzalutamide resistance and provide a novel target in treatment-resistant prostate cancer. Citation Format: Kevin M. Lin, Anna Seidl, Tanner Waldman, Xiang Li, Eva Corey, Adam G. Sowalsky, Leszek Kotula. Alternative splicing of ABI1 by enzalutamide treatment drives tumor plasticity in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4763.

  PublisherDOI

• Abstract 7245: Mechanistic dissection of ABI1 as DNA-binding transcriptional regulator in cancer cells

  Cancer Research · 2026-04-03

  article

  Abstract Background: ABI1 (Abelson interactor-1) is classically recognized as a multifunctional adaptor protein with homeostatic roles in cancer biology. It functions as a tumor suppressor in some cancer such as prostate cancer, yet exhibits oncogenic activity in other cancers such as for example breast cancer. Historically, ABI1 has been studied for its actin-cytoskeleton-associated functions—including cell-cell adhesion, cell motility, and lamellipodia formation—as well as its role in regulating major signaling hubs such as c-Abl, PI3K, and Src. Our recent findings reveal an unanticipated function of ABI1: direct DNA binding mediated by a conserved homeodomain homology region (HHR). This discovery led us to hypothesize that ABI1 may act as a previously unrecognized transcriptional regulator. Here, we sought to define the molecular mechanisms through which ABI1 contributes to transcriptional control. Methods: To determine sequence specificity and genomic occupancy, we performed ChIP using HHR-intact and HHR-mutant ABI1 constructs, complemented by in vitro DNA binding assays using purified proteins. Subcellular fractionation and chromatin enrichment assays assessed ABI1 nuclear localization and association with chromatin. ABI1-interacting transcriptional machinery was identified through co-immunoprecipitation (co-IP). RNA-seq comparing cells expressing wild-type ABI1 versus an HHR-defective DNA-binding mutant defined ABI1-dependent transcriptional outputs. Results: ABI1 binds DNA both in vitro and in vivo and displays reproducible sequence motifs from integrated ChIP and in vitro binding analyses. ABI1 variants containing an intact HHR domain localize preferentially to the nucleus and chromatin fractions. Co-IP studies identify ABI1 as a component of a defined transcriptional complex. RNA-seq analyses reveal that HHR-mediated DNA binding is required for a discrete ABI1-dependent transcriptional program. Conclusions: We identify ABI1 as a novel DNA-binding protein with sequence preference and transcriptional regulatory capacity mediated through its HHR domain. These findings expand the functional repertoire of ABI1 beyond actin regulation and kinase signaling, providing the first mechanistic framework for ABI1-driven transcriptional control. Citation Format: Kate Livingston, XIANG Li, Kevin M. Lin, Leszek Kotula. Mechanistic dissection of ABI1 as DNA-binding transcriptional regulator in cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7245.

  PublisherDOI

• Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer

  Signal Transduction and Targeted Therapy · 2026-05-01

  articleOpen access

  Abstract BCL-2 has been implicated in prostate cancer (PCa) progression and development of castration-resistant disease (CRPC); however, it remains unclear how the BCL-2- and AR-expressing PCa cell populations evolve across the PCa continuum, how AR molecularly regulates BCL-2 and whether BCL-2 represents a common therapeutic target in heterogeneous CRPC. Here we first show the selective induction of BCL-2 by AR pathway inhibitors (ARPIs). Vectra-based quantitative multiplex immunofluorescence (qmIF) and image mass cytometry (IMC) analyses with single-cell resolution in patient PCa and xenograft models reveal markedly increased BCL-2 + (AR + or AR - ) PCa cells in CRPC. Mechanistically, AR represses BCL-2 transcription through several AR binding sites and ARPIs relieve this repression. Therapeutic studies in cells, organoids and xenografts support BCL-2 as a shared vulnerability across diverse CRPC subtypes. A Phase Ib clinical trial (NCT03751436) combining enzalutamide and BCL-2 inhibitor venetoclax demonstrated reduced circulating tumor cells in responding patients. In summary, by integrating high-content single-cell level imaging analyses with mechanistic studies, extensive preclinical therapeutic experiments and a Phase Ib clinical trial, our studies herein elucidate the AR +/- BCL-2 +/- PCa cell subpopulation dynamics and credentials BCL-2 as a vital therapeutic target in heterogeneous CRPC.

  PublisherDOI

• Cardiorenal Syndrome Type 1 Complicated by Uremic Pericarditis and a Small Pericardial Effusion Causing Cardiac Tamponade

  Cureus · 2026-04-23

  articleOpen access

  Cardiac tamponade is typically associated with large pericardial effusions; however, even small effusions can result in significant hemodynamic compromise, particularly in the setting of rapid fluid accumulation and underlying cardiac pathology. This case highlights the diagnostic challenge of identifying low-volume tamponade in a patient with elevated baseline intracardiac pressures. An elderly man was admitted for acute heart failure complicated by cardiorenal syndrome. Following initial diuresis, he developed paradoxically worsening hypotension and pleuritic pain. The absence of a pericardiocentesis, along with clinical recovery, suggested that the patient experienced a spectrum of pericardial constraint rather than definitive, high-pressure tamponade. Severe uremia and a small pericardial effusion suggested uremic pericarditis. Swan-Ganz catheterization showed elevated and relatively concordant diastolic pressures. While diuresis initially complicated the clinical picture, anti-inflammatory therapy with prednisone and colchicine resulted in clinical improvement. This report serves to define the importance of multimodal hemodynamic assessment when classic echocardiographic signs of tamponade are masked by preexisting cardiac remodeling.

  PublisherOA PDFDOI

• Retraction of Deficient LRRC8A-dependent volume-regulated anion channel activity is associated with male infertility in mice

  JCI Insight · 2025-06-22

  articleOpen access
  PublisherDOI

• What makes Reasoning Models Different? Follow the Reasoning Leader for Efficient Decoding

  ArXiv.org · 2025-06-08

  preprintOpen access

  Large reasoning models (LRMs) achieve strong reasoning performance by emitting long chains of thought. Yet, these verbose traces slow down inference and often drift into unnecessary detail, known as the overthinking phenomenon. To better understand LRMs' behavior, we systematically analyze the token-level misalignment between reasoning and non-reasoning models. While it is expected that their primary difference lies in the stylistic "thinking cues", LRMs uniquely exhibit two pivotal, previously under-explored phenomena: a Global Misalignment Rebound, where their divergence from non-reasoning models persists or even grows as response length increases, and more critically, a Local Misalignment Diminish, where the misalignment concentrates at the "thinking cues" each sentence starts with but rapidly declines in the remaining of the sentence. Motivated by the Local Misalignment Diminish, we propose FoReaL-Decoding, a collaborative fast-slow thinking decoding method for cost-quality trade-off. In FoReaL-Decoding, a Leading model leads the first few tokens for each sentence, and then a weaker draft model completes the following tokens to the end of each sentence. FoReaL-Decoding adopts a stochastic gate to smoothly interpolate between the small and the large model. On four popular math-reasoning benchmarks (AIME24, GPQA-Diamond, MATH500, AMC23), FoReaL-Decoding reduces theoretical FLOPs by 30 to 50% and trims CoT length by up to 40%, while preserving 86 to 100% of model performance. These results establish FoReaL-Decoding as a simple, plug-and-play route to controllable cost-quality trade-offs in reasoning-centric tasks.

  PublisherOA PDFDOI

• The Transformative Journey to Becoming a High-Reliability Organization (HRO)

  Physician leadership journal · 2025-08-26 · 1 citations

  article1st authorCorresponding

  Healthcare organizations increasingly aim to become high-reliability organizations (HROs) to ensure patient safety and enhance care quality. Becoming an HRO requires more than operational changes; it necessitates a cultural transformation prioritizing safety and continuous improvement. This review outlines the tactics our organization employed to achieve HRO status, focusing on leadership engagement, safety culture, process improvement strategies, and measurement of progress using a newly created HRO dashboard. Our results indicate significant progress in quality and patient safety, emphasizing the importance of a cohesive strategy encompassing goal-setting, adherence to HRO principles, and effective communication. These efforts have demonstrated the necessity of integrating measurement and strategic planning to drive cultural change and improve patient outcomes.

  PublisherDOI

• S780 Predictors of Weight Loss Following Endoscopic Re-Suturing Post Endoscopic Sleeve Gastroplasty

  The American Journal of Gastroenterology · 2025-10-01

  article1st authorCorresponding

  Introduction: Endoscopic sleeve gastroplasty (ESG) is an effective and durable means for obesity treatment by reducing gastric body volume and impairing gastric emptying. However, a subset of patients experience weight regain or have a plateau in weight loss. The best management strategies for these patients remains unclear. Redo-ESG (R-ESG) is an option to treat weight regain and has been shown to be superior to anti-obesity medications (AOM) alone. While factors associated with weight loss following ESG have been established, predictors of weight loss following R-ESG have not been well studied. Methods: We performed a retrospective analysis of a prospective database including data on all R-ESG procedures performed from January 2013 to May 2024. Inclusion required patients be at least 18 years of age with 2-year follow up data following primary-ESG (P-ESG) and 1-year follow up after R-ESG. Baseline demographic data, medical history, surgical history, procedure factors, medication use, and weight parameters were extracted through chart review. Our primary outcome was factors associated with total body weight loss (TBWL) 6 months following R-ESG. Results: A total of 53 patients were included with a median age of 42 (interquartile range [IQR] 32-52), of which 70% were women. The mean time between P-ESG and R-ESG was 963 days (SD 597.21). 53% of patients were administered a glucagon-like peptide 1 receptor agonist (GLP-1RA) following R-ESG. On univariable regression, greater TBWL at 6 months post-P-ESG and higher body mass index (BMI) prior to P-ESG and R-ESG were associated with greater TBWL at 6 months following R-ESG on univariate analysis. Additionally, TBWL at 1 month following R-ESG was associated with TBWL at 6 months following R-ESG. These variables remained significantly associated with TBWL at 6 months following R-ESG after adjusting for age, sex, BMI, number of sutures used during R-ESG, and use of GLP-1RA and other AOM following R-ESG. Clinically significant TBWL, defined as TBWL >10%, at 6 months following R-ESG was associated TBWL at 6 months following P-ESG on multivariable logistic regression after adjusting for these same covariates. Conclusion: This study identifies factors associated with TBWL following R-ESG. Greater TBWL following P-ESG and early weight loss following R-ESG was associated with 6-month weight loss following R-ESG. These findings mirror predictors of weight loss following P-ESG. This study may help identify patients who will respond to revisional therapy.

  PublisherDOI

• LODESTAR: A single-arm phase II study of rucaparib in solid tumors with pathogenic germline or somatic variants in homologous recombination repair genes.

  Journal of Clinical Oncology · 2025-05-28

  article

  3151 Background: To explore PARP inhibitor (PARPi) utility across solid tumors and identify biomarkers that predict sensitivity. Methods: This single-arm phase II study assessed rucaparib monotherapy in patients with solid tumors and pathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D (Cohort A) or BARD1, BRIP1, FANCA, NBN, RAD51B (Cohort B). The primary endpoint was ORR in Cohort A. Secondary endpoints included DCR, PFS, OS and safety. A scar-based HRD signature (HRDsig) and platinum sensitivity status were explored post-hoc. Results: Fifty-one patients in Cohort A and 12 in Cohort B were evaluable for efficacy. ORR of cohort A was 18% (95% CI 10-30%). A significantly higher ORR was observed with HRDsig+ tumors compared to HRDsig- tumors (32%, 95% CI 15-54, vs. 0%, 95% CI 0-14%, p < 0.01). In the entire study population: DCR of 65% (95% CI 53-76%), mPFS of 5.5 mo (95% CI 3.68-7.82), and mOS of 12.1 mo (95% CI 10.6 – inf). PFS and OS were significantly longer for platinum sensitive tumors (mPFS: 7.8 mo vs. 3.5 mo, p = 0.02; mOS: NR vs 5.45mo, p = 0.01). Tumor histology was not independently predictive of outcome. Tumors with PVs in Cohort A genes were more likely to be HRDsig+ than tumors with PVs in Cohort B genes. Analysis of a large commercial database showed that in non-canonical tumors with BRCA PVs, 30.2% were HRDsig+. Conclusions: Rucaparib has activity in HRDsig+ solid tumors with PVs in HRR genes, regardless of histology. Platinum sensitivity correlated with improved outcomes. Clinical trial information: NCT04171700 .

  PublisherDOI

Recent grants

• Computational Nonlinear Dynamics: Variance Reduction Methods and Numerical Studies of Large, Chaotic, and Noisy Systems

  NSF · $220k · 2014–2018

• CDS&E-MSS: Predictive Modeling and Data-Driven Closure of Chaotic and Noisy Dynamics in Discrete Time

  NSF · $200k · 2018–2023

• Computational Analysis of Large Dynamical Systems

  NSF · $249k · 2009–2013

• NIH Grant F30CA206348

  NIH · $78k · 2018

• PostDoctoral Research Fellowship

  NSF · $108k · 2003–2007

Frequent coauthors

• K. Leigh Greathouse

  Baylor University

  92 shared

• Tia Berry

  92 shared

• Tiffany Bredfeldt

  92 shared

• Kurunthachalam Kannan

  91 shared

• Megan L. Mittelstadt

  91 shared

• Jeffrey I. Everitt

  Duke University

  91 shared

• Shuk‐Mei Ho

  University of Arkansas for Medical Sciences

  91 shared

• Thomas C. Harding

  88 shared

Labs

• Program in Applied MathematicsPI