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Ion channels
Ion channels are among the most important targets in drug discovery. They control the flow of ions across membranes, affecting cell metabolism, communication, and fate (1, 2). When ion channels are not properly regulated, various health issues may arise, such as neuropathies, arrhythmias, and metabolic disorders (3). Despite their significance, developing chemical probes and drug candidates for ion channels can be very challenging. At ALVO lab, we aim to optimize hit compounds from in silico or cell-based screenings while monitoring their pharmacological properties (4, 5). Often, we develop and refine cell-based assays to help us understand the biology of a specific ion channel or a family of channels by modifying chemical probes and other tool compounds (6, 7). We also collaborate with structural biologists to obtain drug-target complexes using Cryo-EM and X-ray crystallography techniques (5).
Understudied kinases
The human kinome is widely recognized as an important target for drug discovery, as kinases are involved in almost every known cellular biochemical pathway (1). More than 100 different FDA-approved kinase inhibitors have been developed, with the majority of them intended for oncology applications (2). Despite these advancements, most efforts in both academia and the pharmaceutical industry have concentrated primarily on the most thoroughly studied kinases (3). This focus has resulted in a large portion of the human kinome remaining understudied, a section often referred to as the “dark kinome” (4). At ALVO lab, our goal is to work collaboratively with researchers to discover and optimize new kinase inhibitors targeting these lesser-known kinases (5, 6, 7). This offers a unique opportunity to investigate previously unexplored biological processes involved in various physiopathological conditions.
Pathogen enzymes
Antimicrobial resistance (AMR) represents a global public health threat, with resistance detected against essentially all antibiotics currently in clinical use (1). This resistance results in infections that are increasingly difficult (or impossible) to treat, thereby worsening clinical outcomes and elevating morbidity and mortality worldwide (2, 3). Addressing the rising threat of antimicrobial resistance requires discovering and developing antibiotics that act on bacterial enzymes essential for microbial survival yet not encoded in the human genome (4). At ALVO lab, our goal is to work closely with biochemists and microbiologists to develop inhibitors of enzymes from bacteria, viruses, and parasites (5, 6) that are absent or largely dissimilar in humans. This offers a unique opportunity to achieve selective killing while minimizing toxicity and bypassing existing resistance mechanisms.
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