About

Welcome to The Berlow Lab in the Department of Biochemistry and Biophysics at the UNC School of Medicine! We are a growing team of biomedical researchers interested in understanding how protein dynamics and allostery mediate crosstalk between stress response pathways in biology and disease.

Research topics

• Biology
• Biochemistry
• Cancer research
• Cell biology
• Chemistry
• Genetics

Selected publications

• BPS2026 – Poly-E and poly-D peptides respond differently to pH shifts and divalent ion concentrations

  Biophysical Journal · 2026-02-01

  article
  PublisherDOI

• BPS2026 – CCDC32 collaborates with the membrane to assemble the AP-2 clathrin adaptor complex

  Biophysical Journal · 2026-02-01

  article
  PublisherDOI

• Sequence-encoded differences in the conformational ensembles of CITED transcriptional activation domains impact coactivator binding

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-01-21

  articleOpen accessSenior authorCorresponding

  Recent advances in predicting and modeling conformational ensembles of intrinsically disordered proteins (IDPs) have provided much needed insights into sequence-ensemble relationships. It is thought that conservation of physicochemical properties, but not the exact identity or order of the amino acids, maintains IDP ensemble properties that are crucial for function. However, detailed experimental studies are still required to fully understand the relationships between sequence and function in IDPs. The human CITED proteins, which are fully disordered transcriptional regulators, share conserved C-terminal transactivation domains (CTADs) that interact with the TAZ1 domain of the transcriptional coactivators CBP/p300. The conserved CTADs harbor amino acid substitutions in regions that are known to be important for interactions of CITED2 with TAZ1, but the effects of these substitutions on TAZ1 binding for the other CITED proteins are unknown. Here, we use solution NMR spectroscopy, circular dichroism, and surface plasmon resonance to characterize the conformational ensembles, dynamics, and interactions of the CITED CTADs. The CTADs are disordered in isolation, although the CITED2 CTAD uniquely displays residual helical structure that is sensitive to ionic strength and protein concentration. In contrast, the CITED1 and CITED4 CTADs remain largely disordered and exhibit more uniform dynamics. Quantitative binding measurements reveal differences in thermodynamics and kinetics for the CTADs' interactions with TAZ1, with CITED2 binding most tightly and CITED4 exhibiting significantly weaker affinity. Our results highlight the sensitivity of IDP conformational ensembles to minor sequence changes and the impacts that changes in IDP structures and dynamics can have on biological functions.

  PublisherOA PDFDOI

• BPS2026 – CCDC32 collaborates with the membrane to assemble the AP-2 clathrin adaptor complex

  Biophysical Journal · 2026-02-01

  article
  PublisherDOI

• BPS2026 – Sequence-encoded multivalent interactions tune the conformational ensembles of intrinsically disordered proteins

  Biophysical Journal · 2026-02-01

  articleSenior author
  PublisherDOI

• Genetic determinants of heart failure susceptibility and response in the collaborative cross mouse population

  Genetics · 2026-01-30 · 1 citations

  article

  Genetic variation and lived experiences shape how our hearts respond to chronic stress and development of heart failure, manifested as compromised pumping function and abnormal hemodynamics. The hallmark of heart failure etiology is excessive stress signals followed by maladaptive structural, electrical, and functional changes to the heart muscle, also known as cardiac remodeling. The specific genetic mechanisms which underly such phenomenon, however, are still unclear, due in part to difficulties in accounting for environmental effects in human population studies. To overcome this challenge, we used the Collaborative Cross (CC) mouse population to investigate heritable susceptibility to cardiovascular stress through chronic β-adrenergic receptor stimulation with the β-agonist isoproterenol (ISO), which targets the common signaling gateway to heart failure, regardless of the particular upstream stressor. Across 8 founder and 63 CC lines, we measured nonfailing and failing heart characteristics represented by cardiac structure and function, organ weights, and cell morphology. Genome-wide QTL mapping detected 49 genome-wide significant loci, collapsing to 20 unique intervals (9 significant for multiple traits and 11 trait-specific), averaging 12.83 Mb in size. To identify high-confidence candidate genes from these loci, we augmented our trait mapping with coding variants drawn from sequencing data, tractability in an in vitro rat cardiomyocyte model, and previously reported protein functions and/or mouse or human phenotypes. This approach recovered both known regulators, such as Hey2, and new candidates. Functional tests in in vitro models highlight 3 candidate genes that modulate hypertrophic growth: Abcb10, Mrps5, and Lmod3. Abcb10 knockdown increased cell size at baseline and further with ISO, consistent with loss of a mitochondrial stress-buffering role. Mrps5 knockdown blunted stress-induced hypertrophy, possibly related to its previously known involvement in oxidative stress regulation. Lmod3 knockdown also attenuated hypertrophy, potentially via actin-assembly control under adrenergic stress. Together, these results reveal heritable pathways of β-adrenergic remodeling in mice and provide an interpretable, translational, and stepwise framework to prioritize candidate genes within broad loci for mechanistic studies of heart failure.

  PublisherDOI

• Abstract 2453 Tuning the conformational ensembles of IDPs through intramolecular and intermolecular interactions

  Journal of Biological Chemistry · 2025-05-01

  articleOpen access1st authorCorresponding

  The intrinsically disordered protein CITED2 is essential in regulating the transcriptional response to oxygen deficiency and other key cellular processes that are important for human health and are often disrupted in disease. CITED2 is a fully disordered protein with interaction motifs positioned throughout the protein sequence that engage a diverse set of molecular partners through dynamic, multivalent interactions. While the interactions of the C-terminal transcriptional activation domain of CITED2 are well-characterized, little is known about the functional roles of the CITED2 N-terminus and its potential impacts on interactions of CITED2 with other transcriptional regulators.

  PublisherOA PDFDOI

• Genetic Determinants of Heart Failure Susceptibility and Response in the Collaborative Cross Mouse Population

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-08 · 2 citations

  preprintOpen access

  Abstract Genetic variation and lived experiences shape how our hearts respond to chronic stress. The specific genetic mechanisms which underly cardiac remodeling, however, are still unclear, due in part to the challenge of accounting for environmental effects in human population studies. To overcome this challenge, we used the Collaborative Cross (CC) mouse population to investigate heritable susceptibility to cardiovascular stress by chronic β-adrenergic receptor stimulation. Across 8 founder and 63 CC lines, we measured cardiac structure and function, organ weights, cell and tissue morphology, and left ventricular gene expression. Genome-wide scans detected 49 genome-wide significant loci, collapsing to 20 unique intervals (nine significant for multiple traits and eleven trait-specific), averaging 12.83 Mb in size. To identify high-confidence candidate genes from these loci, we augmented our trait mapping with associations between loci and gene expression, isoproterenol-dependent transcriptional changes, coding variants drawn from sequencing data, tractability in our in vitro rat cardiomyocyte model, and previously reported protein functions and mouse or human phenotypes. This approach recovered both known regulators, such as Hey2 , and new candidates. Functional tests in in vitro models highlight three candidate genes that modulate hypertrophic growth: Abcb10 , Mrps5 and Lmod3 . Abcb10 knockdown increased cell size at baseline and further with isoproterenol, consistent with loss of a mitochondrial stress-buffering role. Mrps5 knockdown blunted stress-induced hypertrophy. Paradoxical upregulation of Lmod3 after siRNA transfection (validated at the protein level) also attenuated hypertrophy, consistent with reinforcement of actin-assembly control under catecholamine stress. Together, these results reveal heritable pathways of β-adrenergic remodeling in mice and provide an interpretable, translational, and stepwise framework to prioritize candidate genes within broad loci for mechanistic studies of heart failure.

  PublisherOA PDFDOI

• Abstract 2085 Atomic-level insights into the roles of the intrinsically disordered proteins c-Myc and CITED2 in regulating gene expression

  Journal of Biological Chemistry · 2025-05-01

  articleOpen accessSenior author

  Intrinsically disordered proteins (IDPs) are involved in a variety of cellular processes such as the regulation of signaling, transcription, translation, and the cell cycle. Due to their involvement in key cellular processes, IDPs are implicated in many diseases, including cancer. A common feature of IDP interactions is multivalency, which describes the presence of multiple binding sites on an IDP for various binding partners. One example of a multivalent IDP is CITED2, a fully disordered transcriptional regulator that plays a role in cell proliferation, apoptosis, and differentiation, and has been implicated in numerous cancers.

  PublisherOA PDFDOI

• CCDC32 collaborates with the membrane to assemble the AP-2 clathrin adaptor complex

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-05 · 2 citations

  preprintOpen access

  Cells have evolved a variety of assembly chaperones to aid in the difficult process of forming macromolecular complexes in a crowded cytoplasm. Assembly of adaptor protein complex 2 (AP-2), the primary cargo adaptor in clathrin-mediated endocytosis, is regulated by the chaperones AAGAB and CCDC32, whose deletion causes loss of all AP-2 subunits in vivo . AAGAB and CCDC32 are thought to act sequentially to assemble the AP-2 tetramer from its constituent heterodimers. However, the molecular requirements and structural consequences of CCDC32 interaction with AP-2 are not yet understood. Here, using in vitro reconstitution and integrative structural analysis, we describe the molecular mechanism of CCDC32-mediated AP-2 assembly. First, CCDC32 interacts with the appendage domain of the AP-2 α subunit, using the same binding site as canonical endocytic regulators in addition to a novel, yet highly conserved pocket on α. CCDC32 contains cargo sorting motifs normally found in trans-membrane cargo and binds to AP-2 heterodimers using canonical cargo-binding sites. Additionally, two amphipathic helices in CCDC32 bind to the α/σ2 heterodimer. Surprisingly, in solution, we find that CCDC32 prevents complex assembly and actively disassembles AP-2 tetramers. Inhibition requires the amphipathic helices of CCDC32, which also mediate binding to PIP2-containing membranes. The presence of PIP2-containing membrane stabilizes the final stages of assembly. We propose that the membrane acts as a molecular switch to release inhibitory interactions, allowing for full complex assembly to proceed. Using cryo-EM, we visualize an assembly intermediate that mimics the conformation of AP-2 found in vesicles, with CCDC32 bound at both cargo binding sites and both membrane-binding sites, suggesting that assembly leads to deposition of active complexes on the plasma membrane.

  PublisherOA PDFDOI

Frequent coauthors

• H. Jane Dyson

  17 shared

• J. Patrick Loria

  Yale University

  16 shared

• Peter E. Wright

  Scripps Research Institute

  12 shared

• Tatyana I. Igumenova

  Texas A&M University

  9 shared

• Martin Friedlander

  The Lowy Medical Research Institute

  8 shared

• Erin Skeens

  Providence College

  7 shared

• George P. Lisi

  Providence College

  7 shared

• Erin Baker

  University of North Carolina at Chapel Hill

  5 shared

Labs

• The Berlow LabPI

Education

• Ph.D., Molecular Biophysics and Biochemistry

  Yale University

  2011

• B.A., Chemistry

  Johns Hopkins University

  2005