About

Kalina Hristova is a professor of materials science and engineering at Johns Hopkins University. Her research focuses on the structure and assembly of biological membranes, studying the thermodynamic and structural principles that underlie membrane protein folding and signal transduction across membranes. Her lab primarily investigates receptor tyrosine kinases (RTKs), which are often dysregulated in cancer, aiming to understand their function through novel quantitative methodologies she has pioneered. Her work has contributed to a better understanding of RTK activation, membrane-active peptides, and their mechanisms of action, which have applications in drug delivery. Hristova's current research projects include exploring ligand functional selectivity of membrane receptors, the role of the membrane protein interactome, RTK-associated pathogenesis, pH-sensitive peptides for endosomal release, and peptides capable of permeating cellular barriers.

Research topics

• Chemistry
• Biophysics
• Cell biology
• Biology
• Biochemistry

Selected publications

• pH-Responsive peptide nanopores are stabilized by lipid and water-mediated hydrogen bonding networks

  Nanoscale · 2026-01-01

  articleOpen access

  Membrane-spanning nanopores that allow controlled passage of macromolecular cargo across cell membranes can empower many biomedical applications. Such nanopores are formed, in a pH-responsive manner, by the synthetically evolved "pHD peptide" family. pHD peptides fold into amphipathic α-helices, but have many charged and polar residues and are thus not predicted by classical hydropathy analyses to fold into membrane-spanning structures. Yet, when the pH is below ∼6, pHD peptides readily self-assemble into nanopores, even at low concentration. Knowledge of the molecular structure of the pHD peptide pore is needed for further rational design and optimization of nanopore-forming activity targeted to specific membranes and pH conditions. To this end, we have carried out extensive atomistic molecular dynamics simulations to explore the protonation-dependent structure and dynamics of nanopores created by the peptide pHD108. Simulations and graph-based analyses of hydrogen bonding reveal that, in the nanopore, the numerous carboxylate and carboxyamide sidechains form a dense, water-bridged H-bond network across the bilayer. In this network, direct H-bonds between neighboring peptides are few. Instead, the network is dominated by water-bridged intrapeptide interactions and by water-bridged interactions with the headgroups of many lipid molecules with unusual conformations and orientations. The lipids in the H-bond network make critical contributions to nanopore stabilization. These studies reveal a non-classical means of stabilizing nanopores in bilayers formed by highly charged peptides, creating an avenue towards engineering of membrane-embedded structures.

  PublisherOA PDFDOI

• BPS2026 – Reaction coordinate of pH-dependent peptide pore formation

  Biophysical Journal · 2026-02-01

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• BPS2026 – pH-responsive peptide nanoparticles deliver macromolecules to cells via endosomal membrane nanoporation

  Biophysical Journal · 2026-02-01

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• BPS2025 - Membrane nanoporation by pH-responsive acyl-peptides

  Biophysical Journal · 2025-02-01

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  PublisherDOI

• Direct cell reprogramming by a designed agonist inducing HER2-FGFR proximity

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-13

  preprintOpen access

  Growth factor induced receptor dimerization and activation of downstream pathways can modulate cell fate decisions. Here, we investigate the potential of de novo designed synthetic ligands, termed Novokines, to reprogram cell identity by inducing proximity of novel pairs of receptor subunits. We find that a design, H2F, that brings together HER2 (which has no known natural ligand) and the FGF receptor has potent signaling activity. H2F induces robust signaling and reprograms fibroblasts into myogenic cells. Unlike native FGF ligands, H2F selectively activates the MAPK pathway without engaging PLCγ-mediated Ca²⁺ signaling. FRET assays confirm H2F-mediated HER2-FGFR proximity, and phosphoproteomic analysis reveals activation of MAPK effectors. H2F-induced ERK phosphorylation is abolished in cells expressing a kinase-dead FGFR1 (K514M) mutant, confirming the requirement for FGFR catalytic activity. H2F treatment significantly increases myofiber formation from adult patient-derived primary myoblasts, demonstrating its capacity to promote myogenic regeneration. Our findings demonstrate that synthetic receptor pairings can rewire signaling outputs to drive regeneration, providing a programmable platform for cell fate engineering.

  PublisherOA PDFDOI

• Increased thermal stability of FGF10 leads to ectopic signaling during development

  Cellular and Molecular Life Sciences · 2025-04-21 · 2 citations

  articleOpen access

  Fibroblast growth factors (FGFs) control organ morphogenesis during development as well as tissue homeostasis and repair in the adult organism. Despite their importance, many mechanisms that regulate FGF function are still poorly understood. Interestingly, the thermodynamic stability of 22 mammalian FGFs varies widely, with some FGFs remaining stable at body temperature for more than 24 h, while others lose their activity within minutes. How thermodynamic stability contributes to the function of FGFs during development remains unknown. Here we show that FGF10, an important limb and lung morphogen, exists as an intrinsically unstable protein that is prone to unfolding and is rapidly inactivated at 37 °C. Using rationally driven directed mutagenesis, we have developed several highly stable (STAB) FGF10 variants with a melting temperature of over 19 °C more than that of wildtype FGF10. In cellular assays in vitro, the FGF10-STABs did not differ from wildtype FGF10 in terms of binding to FGF receptors, activation of downstream FGF receptor signaling in cells, and induction of gene expression. In mouse embryonal lung explants, FGF10-STABs, but not wildtype FGF10, suppressed branching, resulting in increased alveolarization and expansion of epithelial tissue. Similarly, FGF10-STAB1, but not FGF10 wildtype, inhibited the growth of mouse embryonic tibias and markedly altered limb morphogenesis when implanted into chicken limb buds, collectively demonstrating that thermal instability should be considered an important regulator of FGF function that prevents ectopic signaling. Furthermore, we show enhanced differentiation of human iPSC-derived lung organoids and improved regeneration in ex vivo lung injury models mediated by FGF10-STABs, suggesting an application in cell therapy.

  PublisherOA PDFDOI

• BPS2025 - Study of the assemblies and functions of Eph receptors

  Biophysical Journal · 2025-02-01

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  PublisherDOI

• BPS2025 - Water bridging and lipids with unusual geometries stabilize pH-dependent membrane pores

  Biophysical Journal · 2025-02-01

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  PublisherDOI

• Differential association of EphA2 intracellular regions in biased signaling

  Journal of Biological Chemistry · 2025-03-05 · 2 citations

  articleOpen accessSenior author

  Biased signaling is the ability of a receptor to differentially activate certain signaling cascades in response to different ligands. Our previous work demonstrated that the monomeric ephrinA1 ligand and the widely used dimeric ephrinA1-Fc ligand induced EphA2 receptor tyrosine kinase (RTK) biased signaling. The hypothesis that RTK biased signaling is a consequence of differential interactions between receptor intracellular regions when different ligands are bound to the extracellular region has not been experimentally verified thus far, in part because of the lack of high-resolution structures of full-length RTK oligomers. Here, we compare the effects of deletion of intracellular regions in EphA2 oligomers bound to the biased ligands, monomeric ephrinA1 or ephrinA1-Fc. Our data reveal distinct differences in the intracellular organization of EphA2 oligomers bound to the two ligands, supporting the hypothesis. They also suggest that EphA2 signaling could be modulated by agents that alter interactions between oligomerized EphA2 intracellular regions by binding at sites that can be distant from the ATP-binding pocket.

  PublisherDOI

• Synthesis and luminescence characteristics of yttrium, aluminum and lanthanum borates doped with europium ions (Eu3+)

  Bulgarian Chemical Communications · 2024-04-15 · 2 citations

  articleOpen access1st authorCorresponding

  Inorganic materials doped with rare earth (RE) ions are an object of intense research due to their optical and electrical properties. These materials have the potential for various applications, such as solid-state lasers, active planar waveguides, optical fiber amplifiers, light-emitting diodes (LEDs), displays, ink fillers, security features, etc. RE trivalent ions can emit light from the ultraviolet (UV) to the near-infrared (NIR) regions due to electronic transitions of the 4f-5d levels. Yttrium borate doped with europium ions was prepared by solid-state synthesis in a muffle furnace at 900oC for 4 hours, while lanthanum and aluminum borates doped with europium ions were prepared at 1000oC for 6 hours again in a muffle furnace. The resulting materials are fine white powders. Among the rare earth ions, europium is one of the most commonly used activators because the ions of Eu3+ and Eu2+ can be used as emission sites in the host lattices. Eu3+ ions can produce effective sharp emission peaks in different matrix compositions. Photoluminescence analysis of the samples was performed, based on which the luminescence intensity of the Eu3+ ion was determined through a comparative characteristic. YBO3:Eu3+ phosphor is optically active and chemically stable. It is characterized by a strong orange-red emission at ≈ 591 nm, ≈ 612 and ≈ 696 nm due to the 5D0→7F1 and 5D0→7F2 electronic transitions, respectively. Red emission is also observed for LaBO3:Eu3+ at ≈ 592 and ≈ 615 nm, characterizing the 5D0→7F1 and 5D0→7Fj (j=0, 1, 2, 3, 4) transitions. While aluminum borate doped with europium ion shows intense emission at ≈ 612 nm, making this material suitable for lighting devices. The technique of Fourier transform infrared spectroscopy (FTIR) was used to study the structure of the obtained materials.

  PublisherDOI

Recent grants

• Eph Receptor Heterointeractions in Signaling

  NIH · $3.4M · 2019–2027

• Collaborative Research: Lipid Bilayers and Membrane Active Peptides

  NSF · $260k · 2017–2021

• PROBING PHOSPHORYLATION EVENTS IN BIOLOGICAL MEMBRANES

  NSF · $1.0M · 2021–2025

• Biophysics of protein interactions on membrane surfaces

  NSF · $900k · 2017–2022

• Collaborative Research: Lipid Bilayers and Interfacially Active Peptides

  NSF · $420k · 2010–2014

Frequent coauthors

• William C. Wimley

  Tulane University

  66 shared

• Pavel Krejčı́

  University Hospital Brno

  43 shared

• Elena B. Pasquale

  Discovery Institute

  41 shared

• Bohumil Fafílek

  38 shared

• Taylor P. Light

  Champions Oncology (United States)

  36 shared

• Edwin Li

  The University of Texas at Austin

  32 shared

• Nuala Del Piccolo

  Imperial College London

  29 shared

• Pooja Dudeja

  Institute of Animal Physiology of the Slovak Academy of Sciences

  27 shared

Awards & honors

• Biophysical Society’s Dayhoff award
• Fellow of the American Physical Society
• Fellow of the American Institute for Medical and Biological…