Lema
Rahimi
Sponsor: Jon Sack, Ph.D. MED: Anesth & Pain Medicine The voltage-gated potassium channel subunit 6.4 (Kv6.4) is clinically linked to neuropathic pain. This linkage suggests that drugs targeting Kv6.4 could modulate pain signaling. However, no drugs are known to selectively target Kv6.4. Our aim is to design Kv6.4-selective drugs and test their effects on Kv6.4-mediated electrical signaling. We have designed candidate inhibitor drugs using computational methods, utilizing LatentX to design structurally plausible binders de novo. By designing pore- blocking interfaces targeting Kv6.4-specific residues, we generated candidate Kv6.4 inhibitors. We refined these in silico designs using LigandMPNN, excluding designs that were predicted to interact with the lipid bilayer or other Kv6.4 components. Following this, we validated the designs' sequence and binder-channel interactions with ColabFold, producing high- confidence in silico binders by AlphaFold metrics. We modified designs with a polyhistidine tag to facilitate the expression and purification of nine proteins. We plan to test candidate efficacy through patch-clamp recording Kv6.4 currents in heterologous cells. If these designs selectively inhibit Kv6.4, they will be the first drug candidates to target Kv6.4 and be a tool to determine Kv6.4's function in broader electrical signaling, potentially leading to a new class of analgesics. Exploring NHIP and MeCP2 Co-Expression Patterns in the Human Brain
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Authors:
Lema Rahimi
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Neurodevelopmental disorders, such as Rett syndrome (RTT) and autism spectrum disorder (ASD), result from a complex interplay of genetic and environmental factors. RTT is caused by mutations in the Methyl CpG binding protein 2 gene (MECP2) encoding MeCP2 protein. In contrast, recent studies have linked ASD to altered placental methylation at chromosome 22q13.33, where the neuronal hypoxia inducible, placenta associated (NHIP) gene resides which encodes NHIP protein. NHIP is expressed in the brain, responds to oxidative stress, and appears to influence the expression of ASD-associated genes. Altered expression or methylation of NHIP has been associated with an increased risk of ASD. Although both MeCP2 and NHIP are involved in neurodevelopmental disorders, their functional relationship is not well understood. We hypothesize that NHIP influences the activity of MeCP2 in the human brain through an interaction that may contribute to the development of neurodevelopmental disorders. To test this, we performed immunofluorescent staining using antibodies against MeCP2 and NHIP on RTT patient post-mortem cortical samples and neurotypical controls. Our findings provide evidence of a regulatory interaction between NHIP and MeCP2. Understanding this relationship may offer novel insights into the molecular mechanisms underlying RTT and ASD, contributing to diagnostic or therapeutic strategies. Assessing Changes in Gene Regulation Associated with Chromosome 15q13.3 Deletion Adeena Rahman
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UC Davis / MED: Medical Microbiology&imm / 2026
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Lema Rahimi