Current Projects!

Fragment-Based Drug Discovery (FBDD) is a novel and promising approach to drug design, exemplified by its success in identifying inhibitors for the cancer-related protein Bcl-2. FBDD is computationally less expensive and more cost- effective than standard screening, making it a valuable tool for drug discovery. However, FBDD is often limited by the difficulty of identifying optimal fragments, due to the many criteria a fragment needs to meet, such as suitable molecular weight, solubility, and binding affinity. Thus, there is an unmet need for a tool that predicts the best fragment for a target molecule, especially in medicinal chemistry.

This project explores the use of clozapine, an antipsychotic medication primarily prescribed for treatment-resistant schizophrenia. Our objective is to examine the interactions between clozapine, its metabolites, and specific Human Leukocyte Antigen (HLA) proteins. HLA proteins play a crucial role in the immune system, helping to regulate immune responses. Abnormal interactions with medications like clozapine can lead to severe side effects, such as agranulocytosis, a condition characterized by a dangerously low white blood cell count. Clozapine, known for its efficacy in managing symptoms of schizophrenia that don't respond to other treatments, has a unique pharmacological profile, which makes understanding its interaction with HLA proteins critical. Schizophrenia affects about 1% of the population worldwide, and patients with treatment-resistant forms of this disorder often rely on clozapine as a last resort. This study aims to shed light on the molecular mechanisms of clozapine's side effects, potentially improving treatment safety for this challenging psychiatric condition

This project, in collaboration with the Cunha Lab, explores the role of bacterial metabolites in modulating T-cell activation and their potential links to colorectal cancer. Focusing on key metabolic pathways like histidine metabolism and lipopolysaccharide biosynthesis, we aim to unravel how specific bacterial products influence immune responses and tumor development. Additionally, we leverage docking, molecular dynamics, and other computational chemistry approaches to deepen our understanding of these interactions.

The KRAS gene, originally identified as an oncogene in the Kirsten Rat Sarcoma virus, directs the production of the K-Ras protein. This protein plays a crucial role in transmitting growth signals from outside the cell to its nucleus. Mutations in KRAS can lead to its constant activation, resulting in uncontrolled cell growth and signaling, and thus contributing to the development of cancer. KRAS mutations are present in about 25% of all human cancers, including over 90% of pancreatic cancers and around 25% of lung cancers. Despite being a prevalent oncogene, the lack of distinct binding sites on K-Ras has made it one of the most challenging targets in cancer therapy. Our team is focusing on developing novel compounds that can act as sensors for KRAS activity, potentially opening new avenues for therapeutic intervention.

Our research project investigates the teratogenic effects of methimazole, commonly used in hyperthyroidism treatment. We are concentrating on two major areas: the impact on fetal thyroid development and the induction of oxidative stress and apoptosis in fetal cells. Firstly, we aim to model the interaction between methimazole and thyroid peroxidase (TPO) in the fetal thyroid gland using molecular docking and dynamic simulations. Secondly, we are using computational methods to simulate the biochemical pathways of oxidative stress and apoptosis, assessing the cellular damage and abnormal development methimazole exposure could cause. These studies are critical for understanding methimazole's risks during pregnancy and informing safer therapeutic strategies for hyperthyroidism in expectant mothers.

This research project is centered on investigating the association between GLP-1 agonists, now increasingly used for weight loss and type 2 diabetes management, and the potential increased risk of Papillary Thyroid Cancer (PTC). This inquiry follows a retrospective study suggesting such a link. We aim to computationally analyze the interactions of GLP-1 agonists with thyroid cell receptors and observe the effects on signaling pathways related to cell proliferation and differentiation. Through molecular docking and dynamics simulations, we strive to understand the mechanisms possibly contributing to PTC development in patients using these medications.