Biology subjects

Marathe, A.

Publications and source records attributed to Marathe, A..

4 recordsLinked to original sources

bioRxiv2026

Quantitative Systems Pharmacology Model for Trop-2 Targeting Antibody-Drug Conjugate in Triple-Negative Breast Cancer

TROP2-targeted antibody-drug conjugates (ADCs) have demonstrated promising clinical activity in triple-negative breast cancer (TNBC) as monotherapies; however, therapeutic benefit varies among patients. Combination strategies pairing TROP2-targeted ADCs with immune checkpoint inhibitors are also being investigated. Elucidating the mechanistic drivers of ADC monotherapy variability and enabling the rational development of combination regimens require computational frameworks that integrate ADC pharmacology with tumor-immune interactions. A quantitative systems pharmacology (QSP) model is presented that incorporates an ADC module into our established immuno-oncology model for TNBC. The module captures ADC and payload pharmacokinetics and pharmacodynamics. TNBC heterogeneity is represented by two tumor cell clones with high and low TROP2 expression, informed by prior characterizations, and differential sensitivity to the ADC payload is incorporated as an intrinsic property of each clone. Although generalizable, the model was applied to the TROP2-targeted ADC sacituzumab govitecan (SG, TRODELVY). A virtual patient cohort was generated using Latin hypercube sampling and calibrated against objective response rate (ORR) data from SG Phase I/II TNBC basket trial. The model predicted an ORR of 33.2% consistent with ASCENT study (NCT02574455). Simulations suggest TROP2-mediated delivery contributes modestly to SG efficacy with tumor exposure driven largely by systemically released SN-38 payload being sufficient to induce cytotoxicity. Tumor heterogeneity emerged as a key determinant of response with ORR increasing as the fraction of payload-sensitive clones increased. Overall, this QSP framework for TROP2-targeted ADCs accounts for TNBC heterogeneity and is extendable to other ADCs and targets enabling interrogation of ADC mechanisms of action in conjunction with tumor-immune interactions.

pharmacology and toxicology↗

bioRxiv2026

Divergent venoms among two closely related co-distributed centipede species, Scolopendra morsitans and S. hardwickei in tropical Asia

Venom is an important functional trait that helps predatory animals capture prey. Centipede predatory venoms are complex cocktails of multiple proteins, such as neurotoxins (scoloptoxins), cytotoxins, {beta}-pore-forming toxins, and enzymes. We examined venom phenotypes in two closely related and co-occurring centipede species, Scolopendra morsitans (n=28) and S. hardwickei (n=11), in peninsular India to determine whether their venoms are similar or dissimilar. An integrated proteo-transcriptomic approach was used to characterise the venom phenotypes of the two species across multiple individuals in peninsular India. We used species occurrence records and species distribution models to assess the distributional overlap among these species within the peninsular Indian region. The species showed significant overlap in their current and projected geographical ranges, corresponding with their co-occurrence. We characterised the venom profiles of both species and found that the venoms were cocktails of enzymes, {beta}-pore-forming toxins, and neurotoxins comprising 110 and 84 proteins in S. morsitans and S. hardwickei, respectively. However, the venom composition of both species differed significantly in toxin abundance and species-specific protein repertoires. This indicates trait divergence in venom phenotypes, suggesting that distinct venom compositions may facilitate coexistence among ecologically similar predatory centipedes. The observed variation in venom phenotypes among co-distributed species opens up important avenues for future research into their ecological roles and functional significance. In this study, we provided a detailed account of venom composition across multiple individuals from the species geographic range and highlighted the importance of investigating the role of venom as a trait that could influence species interactions and shape communities in these diverse tropical forests.

ecology↗

bioRxiv2026

Living in the City: Symbiont stability and bacterial compositional and functional plasticity in Miamis urban corals

Increasing urbanization and climate change pose significant threats to coral reefs, highlighting the need to understand the process underlying coral acclimatization in urban environments. Alterations in the microbiome composition represent a key mechanism by which corals adapt to varying environmental conditions. We compared endosymbionts and bacterial communities associated with Siderastrea siderea from urban and offshore Miami reef tracts across three seasons. We found two distinct genera of endosymbiotic Symbiodiniaceae algae, namely Cladocopium and Breviolum, consistently across sites and seasons, with Cladocopium predominating. The stable presence of these symbionts suggests host specificity in S. siderea and highlights the potential advantage of harboring multiple symbionts to enhance survival in diverse environments. In contrast, bacterial diversity exhibited variation across seasons and locations, with a small subset of microbes identified as a core microbiome demonstrating the remarkable plasticity of bacterial communities in response to environmental changes. Differential analysis revealed an increased abundance of Alteromonas and Synechococcus in urban corals, which may contribute to host nutrient acquisition, antibiotic production, and survival in polluted environments. Predicted functional profiles further demonstrated distinct metabolic reorganization of microbial communities between urban and offshore reefs, with urban corals enriched in pathways associated with stress response, pollutant degradation, and nutrient cycling. Together, these findings indicate that while algal symbionts remain stable, bacterial communities undergo both compositional and functional plasticity that likely supports coral persistence in highly urbanized environments.

ecology↗

bioRxiv2025

Range and elevation predict responses to climate change in frogs and lizards in the Western Ghats biodiversity hotspot of peninsular India

Anthropogenic climate change is altering the environment at unprecedented rates with severe consequences for most living organisms. As a result, species may extend, truncate, or shift their ranges in order to adapt to changing conditions. Species Distribution Models (SDMs) provide a data driven approach to predict future distributions under climate change and prioritize areas for conservation. Here, using a 10-year dataset with 4049 occurrence records of frogs from eight families and 27 genera as well as 733 occurrences of lizards from two families and 11 genera across the Western Ghats, we built SDMs to assess the changes in species distributions due to climate change. As expected, the temperature gradient across elevation and seasonality gradient across latitude contribute most to the climatic limits of species distributions. Latitudinal extents of most species were narrower in future predictions compared to the present, but there was little shift in latitudinal positions. On the other hand, most species shifted their distributions towards higher elevations, but the elevational range sizes remained the same. A total of 75 species of frogs (55%) and 15 species of lizards (45%) lose more than half of the suitable area, with few exceptions in both taxa that show an increase. In cases where a shift or increase in distribution was observed, the ability of the species to access and survive in these areas remains uncertain due to discontinuous topography and the presence of sister species. Overall, the frog and lizard fauna of the Western Ghats will be severely affected by climate change in the future due to a loss in climatic suitability.

ecology↗