About

Carla Finkielstein, Ph.D., is a professor at the Fralin Biomedical Research Institute at VTC and holds multiple roles including Director of the Molecular Diagnostics Lab and Interim Director of the Cancer Research Group. Her research focuses on understanding the molecular clocks that regulate cell growth, division, and death, particularly in relation to cancer development and progression. Her lab studies how the body's internal circadian rhythms influence cellular processes and how disruptions in these clocks can lead to mutations and tumor formation. Finkielstein's work emphasizes the relationship between circadian proteins, tumor suppressors, and oncogenes, highlighting the importance of chronotherapeutics—timing treatments to the body's biological clock for improved efficacy. Her research offers foundational insights into how molecular circadian mechanisms impact cancer and explores interdisciplinary approaches to cancer therapy. She has received numerous awards and honors for her contributions to molecular biology and cancer research.

Research topics

• Biology
• Computer Science
• Medicine
• Virology
• Environmental health
• Immunology
• Internal medicine
• Demography
• Environmental science
• Genetics
• Ecology
• Chemistry
• Business
• Biochemistry
• Veterinary medicine
• Pathology
• Stereochemistry
• Environmental engineering
• Cell biology
• Cancer research
• Neuroscience
• Nursing
• Philosophy
• Family medicine

Selected publications

• White-tailed deer milk exhibits SARS-CoV-2 neutralizing antibodies and synergistic mechanisms that contribute to rapid viral RNA degradation

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-12

  articleOpen accessSenior authorCorresponding

  Abstract White-tailed deer (WTD) represent the most significant SARS-CoV-2 wildlife reservoir in North America, yet the role of antiviral mechanisms in vertical transmission remains unexplored. We investigated SARS-CoV-2 antibody responses and viral stability in milk from lactating WTD and humans to characterize species-specific antiviral mechanisms. SARS-CoV-2 neutralizing antibodies were detected in milk and serum in WTD specimens using complementary immunoassays, providing the first evidence of humoral immune responses in wildlife milk. Despite antibody presence indicating prior SARS-CoV-2 exposure, viral RNA was undetectable in all WTD milk samples. This pattern aligns with observations in human milk, where viral RNA was also undetectable both during active infection (when nasal swabs were positive) and during antibody-positive periods following recovery. In vitro stability studies revealed striking species differences: all SARS-CoV-2 variants (A, B.1.1.7, BA.1.1.529) rapidly degraded in WTD milk within 30 min at physiological temperatures, while remaining mostly stable in human milk for up to 60 min. Biochemical characterization identified multifactorial degradation mechanisms in WTD milk, including 5-20 fold elevated mineral concentrations (sodium, magnesium, phosphorus, and potassium), enhanced protease activity, and increased lactoperoxidase levels. Individual mineral supplementation revealed variant-specific susceptibilities, with B.1.1.7 showing pronounced sensitivity to ionic stress. Mechanistic studies demonstrated synergistic effects between elevated ionic concentrations and proteolytic activity, with heat-labile and heat-stable degradation pathways contributing to viral inactivation. These findings reveal that WTD milk possesses intrinsic antiviral properties fundamentally different from human milk, representing an evolutionary adaptation that may impact viral persistence and transmission dynamics in wildlife populations. These findings reveal antiviral mechanisms in WTD milk that represent a previously unrecognized component of pathogen control in wildlife reservoirs, with important implications for understanding wildlife-pathogen interactions and zoonotic risk assessment. Author Summary White-tailed deer (WTD) have become the primary wildlife reservoir for SARS-CoV-2, with millions of infected animals across North America. Despite this significance, the presence of protective antibodies and viral behavior in WTD milk remained unexplored. We collected milk samples from lactating WTD during hunting seasons to investigate whether WTD produce neutralizing antibodies similar to those found in human milk and to examine how the virus behaves in this biological fluid. Our analysis revealed that WTD milk contains antibodies capable of neutralizing SARS-CoV-2. When we compared viral stability between WTD and human milk, we observed that WTD milk rapidly degrades viral genetic material within 30-40 min, while the same virus remains stable in human milk for over an hour. We identified that WTD milk contains mineral concentrations 5-20 times higher than human milk, including elevated levels of sodium, magnesium, and potassium, along with enhanced enzyme activity that breaks down viral components. These findings indicate that WTD milk functions as a protective barrier rather than a transmission route. This has implications for understanding viral persistence in wildlife populations and assessing potential risks to human health. Our work demonstrates that deer milk possesses multiple biological defense mechanisms that may protect offspring from viral infections, contributing to our understanding of wildlife immunity and pandemic preparedness.

  PublisherOA PDFDOI

• 380 Uncharacterized MYH9 Germline Mutations in a Microcystic Adnexal Carcinoma Mimicker: Benign Deep Syringoid Ductal Proliferation (BDSDP) with Elastic Fiber Aggregation

  Laboratory Investigation · 2026-03-01

  articleSenior author
  PublisherDOI

• Pancreatic cancer extracellular vesicles carry a time-of-day-regulated miRNA cargo that disrupts the skeletal muscle clock and bioenergetics

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-04

  articleOpen accessSenior authorCorresponding

  ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis, aggravated by cachexia, a systemic wasting syndrome whose molecular mediators remain incompletely defined. Circadian disruption is a further hallmark of PDAC, yet a shared mechanistic basis between these two features has not been established. Here we show that the PDAC secretome, and the small extracellular vesicles (sEVs) it carries, are sufficient to disrupt the circadian clock in independent reporter cell lines and in differentiated myotubes, and to induce myotube atrophy. PANC-1 sEV release and miRNA cargo display pronounced time-of-day variation, with the cargo resolving into two functionally distinct pools: a rhythmically secreted subset, whose release is phase-coordinated and which transmits time-of-day information to the recipient tissue, and a constitutively secreted subset that, although non-rhythmic at the source, is itself capable of perturbing the recipient circadian clock. Individual miRNAs drawn from both pools exert distinct and non-redundant effects on circadian period and myotube diameter. Seahorse extracellular flux analysis further reveals that these miRNAs reprogram mitochondrial respiration and substrate utilization along three divergent trajectories, energetic, high-metabolic, and glycolytic, rather than along a single bioenergetic axis. Intersecting the tumor sEV secretome with serum sEV miRNAs from a pancreatic cancer patient cohort and with the miRNA-Seq landscape of 495 PDAC tumors defines a stable, broadly tumor-abundant, patient-detectable miRNA signature that collectively regulates circadian, proteostatic, and cachexia-relevant gene networks. Across these orthogonal datasets, hsa-miR-27b-3p emerges as a node within the rhythmically secreted pool: consistently detected in patient serum, ranked among the top 50 most abundant miRNAs in >90% of these tumors, and individually sufficient to shorten the circadian period, drive myotube atrophy comparable to dexamethasone, and impose an energetic mitochondrial phenotype. Together, these findings identify PDAC sEV miRNAs as temporally organized mediators coupling circadian disruption, muscle bioenergetics, and cachexia-relevant muscle reprogramming.

  PublisherDOI

• Sample pooling approaches simulated under resource scarcity, lapses in testing capacity, and rapid processing demands for surveillance testing: a data-driven performance comparison

  BMC Infectious Diseases · 2026-01-30

  articleOpen access

  Sample pooling is a critical strategy to meet increased testing demand and conserve resources in surveillance testing. Much of its effectiveness depends on how well optimized the pool size is to the prevalence of infection in the sampled population, which can be difficult to anticipate in many circumstances. Multiple methods exist to better optimize pooling, with unique trade-offs. Pooling optimization methods were simulated to examine trade-offs between surveillance priorities and operational characteristics using SARS-CoV-2 surveillance data and workflows generated by the Virginia Tech Molecular Diagnostics Laboratory under varying capacity conditions. All in-house validation procedures were designed and established exclusively under CLIA to ensure full control of the analytical framework and to accurately reflect true capacity constraints. We used binary surveillance data to run Monte Carlo simulations (MCS) comparing conservative and large fixed pools, historical prevalence optimization (HPO), prevalence estimation testing (PET), truly optimized pooling, and individual testing. Median test counts from the MCS fed a discrete-event simulation (DES) that assessed processing time at different lab capacities under surveillance and outbreak conditions. We then used the combined performance results to build a classification tree to guide method selection under different testing priorities and constraints. MCS results indicated that small pools (4 samples), HPO, and PET resulted in test counts that were not statistically different from truly optimized pooling (p > 0.05). The DES showed that pooling methods generally performed comparably to individual testing in processing time at low laboratory capacity, but individual testing became faster as capacity increased. Across capacity conditions, individual testing processed fewer than 500 daily samples more quickly, yet it demanded more hands-on time than pooling. Large-scale surveillance favored pooled methods, which were quicker under most conditions, while outbreak scenarios often favored individual testing when capacity wasn’t highly limited. Machine learning analysis highlighted surveillance priorities and sample intake as key determinants in selecting the best pooling optimization method for the given circumstance. This study demonstrates the importance of maintaining multiple pooling optimization approaches and adapting strategies to match evolving demands and potential constraints in surveillance testing. Not applicable.

  PublisherDOI

• Circadian Disruption Drives Extracellular Matrix Remodeling to Facilitate Pulmonary Metastatic Colonization

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-23

  articleOpen accessSenior authorCorresponding

  SUMMARY Circadian clocks impose temporal architecture on signaling networks, and disruption of this architecture predisposes to cancer metastasis. Through direct pharmacological and genetic perturbation of core clock components, we establish that circadian desynchronization in mouse lung fibroblasts eliminates temporal migration gating, creating constitutive motility responses to TNF-α and TGF-β, and identify YAP/TEAD as the obligate, non-redundant convergence node through which clock-regulated ECM mechanical signals and cytokine-driven transcriptional programs jointly drive cellular motility. Chronic jet lag (CJL) in mice generates nocturnal TNF-α elevation (ZT12-21) that drives sustained matrix metalloprotease expression while simultaneously reorganizing Hippo and TGF-β signaling toward temporal convergence during daytime hours, enabling YAP/TEAD-dependent transcription to synergize with TGF-β signaling and drive epithelial-to-mesenchymal transition (EMT) programs that normally remain temporally restricted. Functional validation demonstrates CJL doubles metastatic colonization incidence (40% to 90%) following B16F10 melanoma inoculation. Critically, established metastases amplify these molecular changes: metastatic burden under CJL creates maximal TGF-β expression (ZT15-21), constitutive YAP activity, and sustained EMT marker expression, while eliminating M1/M2 macrophage temporal organization. Analysis of TCGA-SKCM metastatic melanoma datasets confirms that clock-disrupted human tumors exhibit selective strengthening of YAP/TAZ, EMT, and inflammatory pathway coupling, establishing that this convergence architecture is conserved in human disease. Together, these findings demonstrate that circadian disruption transforms from a facilitator of initial metastatic colonization into a driver of progressive metastatic burden by eliminating the temporal segregation that normally constrains pro-metastatic programs to discrete, non-overlapping windows, creating self-perpetuating cycles wherein pathway convergence facilitates colonization and established tumors amplify pro-metastatic signaling to maintain permissive microenvironmental conditions.

  PublisherDOI

• Circadian regulation of extracellular vesicle biogenesis, composition, and release

  npj Biological Timing and Sleep · 2025-11-03 · 3 citations

  articleOpen accessSenior author

  Circadian rhythms in mammals are governed by cell-autonomous oscillators that synchronize physiological functions through central and peripheral communication. Extracellular vesicles (EVs) mediate intercellular and systemic signaling, with time-of-day-dependent release and cargo composition regulated by the circadian clock. This regulation involves both transcriptional and post-transcriptional mechanisms affecting genes involved in EV biogenesis. Studies in diverse models show EVs impact physiological and pathological processes, including inflammation, cardiovascular disease, chronic kidney disease, and cancer. EVs also serve as important biomarkers, especially in cancer. The accompanying article explores how clock proteins regulate multiple aspects of EV biology and highlights the significance of circadian dysregulation in EV-associated pathologies. Understanding EV-mediated signaling within the framework of circadian rhythms is critical for improving disease diagnosis, informing treatment strategies, developing therapeutic applications, and enhancing the diagnostic utility of EVs. This insight may pave the way for novel chronotherapy approaches in clinical practice.

  PublisherOA PDFDOI

• The PER2:BRCA1:POU2F1(OCT-1) ternary complex represents a multi-component scaffold model for circadian gene regulation

  Neurobiology of Sleep and Circadian Rhythms · 2025-11-30

  articleOpen accessSenior authorCorresponding

  The circadian clock component PER2 coordinates daily oscillations in gene expression across multiple tissues, yet its role in assembling multi-protein regulatory complexes remains incompletely understood. Here, we report that PER2 nucleates a ternary complex with the tumor suppressor BRCA1 and the transcription factor POU2F1(OCT-1) to impose circadian control on target gene promoters. Using bacterial two-hybrid screening, we identified BRCA1 as a novel PER2-interacting protein. Biochemical mapping revealed that PER2 engages BRCA1 through multiple discrete binding interfaces: PER2 spanning residues 356-574 and 683-872 interact with both the N-terminal (1-400) and C-terminal BRCT(1670-1863) domains of BRCA1. Structural modeling predicted 361 residue contacts between PER2 and BRCA1, substantially more than the 74 contacts predicted for PER2:POU2F1(OCT-1), indicating differential affinities that enable ordered complex assembly. Sequential pull-down assays demonstrated that PER2, BRCA1, and POU domain form a stable ternary complex in vitro , with POU2F1(OCT-1) serving as the DNA-binding platform. Electrophoretic mobility shift assays revealed that pre-assembly of PER2 with POU domain inhibits DNA binding, while BRCA1 is essential for stabilizing PER2 recruitment to DNA-bound POU2F1(OCT-1). Using ESR1 as a functional readout, we demonstrate that this ternary complex directly regulates promoter activity. Circadian transcriptome analysis reveals that Esr1 exhibits robust clock-dependent oscillations that are abolished in Per1/2 double-knockout mice, while Pou2f1 and Brca1 maintain constitutive expression. These findings establish PER2 as a circadian scaffold that assembles multivalent protein complexes to temporally gate transcription, providing mechanistic insight into how circadian disruption can influence target gene expression. • PER2 directly interacts with BRCA1 through multiple discrete binding interfaces. • PER2, BRCA1, and POU2F1 (OCT-1) form a ternary complex that coordinately regulates ESR1 transcription. • An ordered assembly of POU2F1 (OCT-1), BRCA1, and PER2 is required at the ESR1 promoter for proper transcriptional regulation. • ESR1 expression exhibits circadian oscillations dependent on functional PER2 but not on rhythmic BRCA1 or POU2F1 expression. • Disruption of the ternary complex by BRCA1 mutations or circadian misalignment may mechanistically link cancer risk to circadian disruption.

  PublisherDOI

• Oral dosage forms for drug delivery to the colon: an existing gap between research and commercial applications

  Journal of Materials Science Materials in Medicine · 2025-03-04 · 7 citations

  reviewOpen access

  Oral drug administration is the preferred route for pharmaceuticals, accounting for ~90% of the global pharmaceutical market due to its convenience and cost-effectiveness. This study provides a comprehensive scientific and technological analysis of the latest advances in oral dosage forms for colon-targeted drug delivery. Utilizing scientific and patent databases, along with a bibliometric analysis and bibliographical review, we compared the oral dosage forms (technology) with the specific application of the technology (colon delivery) using four search equations. Our findings reveal a gap in the publications and inventions associated with oral dosage forms for colon release compared to oral dosage forms for general applications. While tablets and capsules were found the most used dosage forms, other platforms such as nanoparticles, microparticles, and emulsions have been also explored. Enteric coatings are the most frequently applied excipient to prevent the early drug release in the stomach with pH-triggered systems being the predominant release mechanism. In summary, this review provides a comprehensive analysis of the last advancements and high-impact resources in the development of oral dosage forms for colon-targeted drug delivery, providing insights into the technological maturity of these approaches.

  PublisherOA PDFDOI

• Enhancing a low-cost, minimally invasive screening test for dihydropyrimidine dehydrogenase mutations linked to 5-fluorouracil sensitivity by integrating computational mutation predictions.

  Journal of Clinical Oncology · 2025-01-27

  articleSenior author

  226 Background: 5-Fluorouracil (5-FU), a common chemotherapy for solid tumors, is metabolized primarily by dihydropyrimidine dehydrogenase (DPD), encoded by the DPYD gene. With > 200 known variants, individuals with nonfunctional DPYD alleles exhibit impaired 5-FU metabolism and are at risk of severe toxicity. Approximately 35% of the population has partial DPD deficiency, and 0.2% completely lack enzymatic activity. Despite this, DPYD genotyping is not standard practice. This study evaluates the use of non-invasive saliva samples for DPYD genotyping and combines AI-based molecular prediction modeling to search for novel variants within DPYD coding region. Saliva samples were collected from fifty-six healthy individuals and from gastrointestinal (GI) cancer patients including a family cohort of nineteen individuals and three unrelated patients undergoing chemotherapy. Methods: gDNA was sequenced for nine DPYD variants reported to reduced or abrogate DPD activity: c.1905+1G > A, c.1679T > G, c.2846A > T, c.1129-5923C > G, c.1236G > A, c.299_302delTCAT, c.703C > T, c.2983G > T, and c.557A > G. cBioPortal was utilized to search the TCGA database for studies involving colon cancer patients with novel DPYD mutations exhibiting a total FIS score of at least 2 or identified through 3D modeling of DPD using PyMol based on their proximity to or the presence of polar contacts within the active site. Putative pathogenic mutations were analyzed using AlphaMissense and ChimeraX to assign a RSMD score, assessing their potential negative impact on DPD function. Results: Computational studies identified three mutations in DPYD from TCGA colon cancer patients with an unknown impact on DPD and a FIS greater than 4 (c.198G > C/T, c.2161G > A, c.2185G > A), suggesting potential disruption of its function. Four mutations (c.424T > G, c.427T > G, c.2460G > C, c.2909C > A) were identified through protein modeling using PyMol, but only two had a FIS greater than 2. Of these seven identified mutations, four (c.198G > C/T, c.2161G > A, c.2185G > A, c.2909C > A) also scored highly using AlphaMissense and ChimeraX. In silico prediction models from VarSome listed c.2185G > A as Pathogenic Moderate and c.2909C > A as Pathogenic Very Strong. Sequencing of saliva samples indicated mutations c.1129-5923C > G and c.1236G > A were present in four and three volunteers, respectively, and c.1905+1G > A in one case. Mutations identified in GI cancer patients were c.1129-5923C > G and c.1236G > A. Conclusions: By combining computational modeling with the analysis of naturally occurring mutations in colon cancer patients, we have successfully identified potentially pathogenic mutations in the DPYD gene. This information can enhance existing clinical diagnostic tests, providing a more comprehensive assessment of DPYD mutations, including novel variants.

  PublisherDOI

• Uncharacterized <i>MYH9</i> Germline Mutations in a Microcystic Adnexal Carcinoma Mimicker: Benign Deep Syringoid Ductal Proliferation (BDSDP) with Elastic Fiber Aggregation

  medRxiv · 2025-08-05

  preprintOpen accessSenior author

  Abstract Importance Microcystic adnexal carcinoma (MAC) is a rare, locally aggressive sweat gland neoplasm sometimes misdiagnosed due to its histologic similarities to benign adnexal proliferations. MYH9-associated elastin aggregation syndrome (MALTA) is an inherited condition characterized by benign MAC-like ductal lesions and by abnormal elastic fiber deposition. Objective To report previously uncharacterized heterozygous germline mutations in the MYH9 gene in a patient presenting benign deep syringoid ductal proliferations and papillary dermal elastic fiber aggregation. Design, Setting, Participants Clinical report with genetic and structural analysis. Dermatology outpatient. A male in their 20’s presenting with long-standing, stable erythematous nodules on the right infraorbital region and left zygomatic arch. Genetic testing of first-degree relatives and structural simulations were performed to assess variant impact. Main Outcomes and Measures Histological evaluation of the patient’s lesions revealed benign deep syringoid ductal proliferations with papillary dermal elastic fiber aggregation, distinguishing them from microcystic adnexal carcinoma. Germline genetic testing identified three heterozygous MYH9 variants, two previously uncharacterized, all showing Mendelian segregation in first-degree relatives and associated with structural rearrangement. Results Histologic evaluation of the facial lesions revealed keratin-filled microcysts and deep dermal and subcutaneous cords with ductal structures resembling MAC. Immunohistochemistry showed apocrine differentiation (EMA+/CD15+/GCDP+) and basaloid myoepithelial cells positive for p63. No evidence of perineural invasion was observed. Elastic tissue staining showed dense, ball-like aggregates of elastic fibers in the papillary dermis. Germline testing identified c.1363G&gt;A (p.Gly455Ser) in the myosin head domain, and c.4490G&gt;A (p.Arg1497Gln) and c.4876A&gt;G (p.Ile1626Val) in the tail domain of Myosin-9. Saliva-based testing confirmed Mendelian segregation in multiple first-degree relatives. Missense mutations were predicted to alter the coiled-coil structure, potentially disrupting chain interactions and affecting the motif’s parallel versus antiparallel orientation. Conclusions and Relevance This case broadens the phenotypic and genotypic spectrum of MALTA syndrome and introduces the diagnostic term: benign deep syringoid ductal proliferation (BDSDP) with elastic fiber aggregation. The findings underscore the diagnostic challenges in distinguishing BDSDP from MAC and highlight the critical role of integrating histopathologic, immunohistochemical, and genetic data in accurate diagnosis. These results support the need for further investigation into MYH9-associated adnexal neoplasia and its underlying molecular mechanisms. Key Points Question How do germline MYH9 variants contribute to the pathogenesis of benign deep syringoid ductal proliferations with elastic fiber aggregation, a phenotype that clinically and histologically mimics microcystic adnexal carcinoma? Findings Genetic analysis revealed two previously unreported heterozygous variants in the MYH9 gene: c.1363G&gt;A (p.Gly455Ser), located in the myosin head domain, a region previously associated with MALTA syndrome, and a variant in the myosin tail domain, c.4490G&gt;A (p.Arg1497Gln). A third mutation, c.4876A&gt;G (p.Ile1626Val), was also detected. All three variants demonstrated Mendelian segregation from the parents, were identified in multiple family members, and were predicted to cause structural perturbations. Meaning These findings provide strong evidence for a heritable contribution of these mutations to the observed phenotype. The presence of these MYH9 variants highlights a potential functional impact on protein structure and activity. This pattern supports the hypothesis that MYH9 mutations may underlie or modify the pathogenesis of benign syringoid ductal proliferations, expanding the known spectrum of MYH9-associated conditions and offering a molecular basis for improved diagnosis and familial risk assessment.

  PublisherOA PDFDOI

Recent grants

• CAREER: Circadian Control of Cell Division and Homeostasis

  NSF · $1.1M · 2009–2014

• A combined mathematical and bioengineering approach to elucidate the contribution of circadian factors in the cellular response to genotoxic stress

  NSF · $750k · 2015–2020

Frequent coauthors

• Daniel G. S. Capelluto

  44 shared

• Tetsuya Gotoh

  Virginia Tech

  28 shared

• Alessandro Ceci

  Biomedical Research Institute

  27 shared

• Katherine L. Brown

  Weill Cornell Medicine

  20 shared

• Michael Friedländer

  17 shared

• James Weger‐Lucarelli

  Virginia Tech

  16 shared

• Anne M. Brown

  Center for Discovery

  16 shared

• Raúl González

  14 shared

Labs

• Advancement TeamPI

Education

• Ph.D.

  Universidad de Buenos Aires, School of Natural Sciences

  1998

• Bachelor of Science, Cellular and Molecular Biology

  Universidad de Buenos Aires - School of Natural Sciences

  1992

Awards & honors

• Ut Prosim Scholar Award, Virginia Tech (2021)
• Luther and Alice Hamlett Junior Faculty Fellow (2020)
• J. Shelton Horsley Research Award, Virginia Academy of Scien…
• Mitzi L. Frank Memorial Endowed Fund (2018)
• Mary Louise Olds Andrews Cancer Award, Virginia Academy of S…