Krzysztof Krajewski
· Professor & Director of Peptide Synthesis CoreVerifiedUniversity of North Carolina at Chapel Hill · Physiology and Pharmacology
Active 1981–2026
About
Krzysztof Krajewski is a Professor and Director of the Peptide Synthesis Core at the UNC School of Medicine, Department of Biochemistry and Biophysics. His research focuses on peptide chemistry and synthesis, histone post-translational modifications (PTMs), and the applications of peptides in biochemical assays. He has extensive experience in synthesizing peptides up to 80 residues long, utilizing automated microwave-assisted Fmoc Solid Phase Peptide Synthesis (SPPS), and offers a wide range of chemical modifications including acetylation, methylation, phosphorylation, fluorescent labeling, biotinylation, PEG spacers, incorporation of D-amino acids, unnatural amino acids, and stable isotopes. His core facility supports applications in antibody production, enzyme assays, ligand-binding studies, and quantitative biophysical analyses such as NMR, ITC, and crystallography, ensuring high-quality peptides tailored to diverse research needs.
Research topics
- Genetics
- Biology
- Computational biology
- Computer Science
- Evolutionary biology
- Artificial Intelligence
- Nanotechnology
- Cell biology
- Chemistry
- Botany
- Virology
- Medicine
Selected publications
bioRxiv (Cold Spring Harbor Laboratory) · 2026-04-24
articleOpen accessAbstract Bromodomain-containing protein 4 (BRD4) is an acetyl-lysine reader protein implicated in transcriptional control and oncogenesis, yet how its tandem bromodomains (BD1-2) contribute to nucleosomal engagement remains unresolved. Here we show that the tandem bromodomains of BRD4 cooperatively engage poly-acetylated histone H4 tails and nucleosomes in vitro and promote chromatin association in human cells. In stringent peptide pull-down and nucleosome-based biolayer interferometry assays, isolated BRD4 bromodomains bind weakly to poly-acetylated histone peptides and nucleosomes, whereas the tandem BD1-2 module binds much more robustly. These results closely mirror our observations in mammalian cells, where truncations lacking either bromodomain or pocket-disrupting mutations in either domain reduced chromatin association, with dual pocket disruption causing the strongest defect. In the BRD4 short isoform (BRD4-S), maximal chromatin association additionally required the region C-terminal to the BD2, which contains the basic residue-enriched interaction domain (BID) and extraterminal domain (ET), consistent with a multivalent chromatin engagement mechanism beyond the bromodomains alone. Functionally, dual pocket disruption attenuated BRD4-S-dependent breast cancer phenotypes, including impaired growth and reduced transwell migration. Together, these findings define how tandem bromodomains and adjacent BRD4-S regions cooperate to stabilize chromatin residence and inform therapeutic strategies aimed at more precisely disrupting BRD4 function. Graphical Abstract
Nucleic Acids Research · 2025-07-08 · 1 citations
articleOpen accessPlant homeodomain (PHD) fingers are critical effectors of histone post-translational modifications (PTMs), regulating gene expression and genome integrity, and are frequently implicated in human disease. While most PHD fingers recognize unmodified and methylated states of histone H3 lysine 4 (H3K4), the specific functions of many of the over 100 human PHD finger-containing proteins are poorly understood. Here, we present a comprehensive analysis of one such poorly characterized PHD finger-containing protein, PHRF1. Using biochemical, molecular, and cellular approaches, we demonstrate that PHRF1 robustly binds to histone H3, specifically at its N-terminal region. Through integrating RNA-seq and proteomic analyses, we show that PHRF1 regulates transcription and RNA splicing and plays a critical role in DNA damage response (DDR). Crucially, we show that a cancer-associated mutation in the PHRF1 PHD finger (P221L) abolishes its histone interaction and fails to rescue defective DDR in PHRF1 knockout cells. These findings underscore the importance of the PHRF1-H3 interaction in maintaining genome integrity and provide new insight into how PHD fingers contribute to chromatin biology.
Biomolecules · 2025-08-25 · 2 citations
articleOpen accessThe clinical use of 1,25-dihydroxycholecalciferol (1,25D3), the active form of vitamin D3, is limited by its calcemic side effects and rapid metabolic degradation. To overcome these limitations, we designed novel vitamin D analogs with extended, rigidified, and branched side chains. Among them, PRI-1938, featuring a 5,6-trans triene system and 22,24-all-trans side-chain geometry, demonstrated markedly enhanced resistance to enzymatic catabolism. In vitro assays revealed that metabolic conversion of PRI-1938 by the nonselective cytochrome P450 3A4 (CYP3A4) enzyme was ca. 4-fold lower than that of the previously obtained PRI-1906 and over 9-fold lower than 1,25D3. All new analogs, including PRI-1927 and PRI-1937, exhibited significantly higher stability toward mitochondrial cytochrome P450 24A1 (CYP24A1), the vitamin D-selective catabolic enzyme, than that of 1,25D3. Molecular modeling and quantum mechanical calculations indicated that PRI-1938 adopts a highly stable conformation in the CYP24A1 active site, stabilized by four hydrogen bonds and multiple hydrophobic interactions. The spatially optimized interaction network reduces access to the catalytic heme, resulting in the lowest observed metabolic conversion. These findings highlight the critical role of the side-chain geometry in modulating metabolic stability and support the further development of PRI-1938 as a promising anticancer vitamin D analog.
Penal Exceptionalism in Central Europe
Crime and Justice · 2025-08-14 · 2 citations
article1st authorCorrespondingThe countries of Central Europe have for many years occupied a leading position in Europe in imprisonment rates and the use of imprisonment. The reasons for this may be connected to having been under authoritarian rule for many years. Another factor may be the penal populism that is influential throughout the world but has specific features in Central Europe. One such explanation, “penal nationalism,” argues that exceptionalism results from a distinctive brand of nationalist attitudes, especially towards the European Union. Social welfare policies, egalitarianism, income inequality, and residents’ trust in one another and the state, among other factors, have repeatedly been shown to be associated with imprisonment rates. Central European countries usually score low, sometimes very low, on these measures. Other more prosaic explanations relate to national laws and policies that increase punitiveness generally, and the use of imprisonment, even though that was not their purpose. None of these considerations by itself explains why imprisonment rates are, and long have been, comparatively high in Central Europe, especially relative to Western Europe, but provide elements from which fuller explanations may emerge.
UNC Libraries · 2025-05-20
articleOpen accessTight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the on/off state of cell identity genes such as the Hox factors. Polycomb group complexes repress target genes, whereas trithorax group complexes are required for their expression. Although trithorax and its orthologs function as methyltransferases specific to histone H3 lysine 4 (H3K4), there is no direct evidence that H3K4 regulates Polycomb group target genes in vivo. Using histone gene replacement in <em>Drosophila</em>, we provide evidence of two key roles for replication-dependent histone H3.2K4 in Polycomb target gene control. First, we found that H3.2K4 mutants mimic H3.2K4me3 in antagonizing methyltransferase activity of the PRC2 Polycomb group complex. Second, we found that H3.2K4 is also required for proper activation of Polycomb targets. We conclude that H3.2K4 directly regulates Polycomb target gene expression.
Nucleosome context regulates chromatin reader preference
UNC Libraries · 2025-11-14
articleOpen accessChromatin is more than a simple genome packaging system but rather locally distinguished by histone post-translational modifications (PTMs) that can directly change nucleosome structure and/or be “read” by chromatin-associated proteins to mediate downstream events. An accurate understanding of histone PTM binding preference is vital to explain normal function and pathogenesis and has revealed multiple therapeutic opportunities. Such studies most often use histone peptides, though these cannot represent the full regulatory potential of nucleosome context. Here we apply a range of complementary and easily adoptable biochemical and genomic approaches to interrogate fully defined peptide and nucleosome targets with a diversity of mono- or multivalent chromatin readers. In the resulting data, nucleosome context consistently refined reader binding, and multivalent engagement was more often regulatory than simply additive. This included abrogating binding of the Polycomb group malignant brain tumor (MBT) protein L3MBTL1 to lysine methylated histone tails and confirmation that the CBX7 chromodomain and AT-hook-like motif (CD-ATL) tandem act as a functional unit to confer specificity for H3K27me3. These in vitro nucleosome preferences were confirmed by in vivo reader-CUT&RUN genomic mapping. Such data confirms that more representative chromatin substrates provide greater insight into biological mechanism and human disease.
Nucleosome context regulates chromatin reader preference
bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-29 · 3 citations
preprintOpen accessABSTRACT Chromatin is more than a simple genome packaging system, and instead locally distinguished by histone post-translational modifications (PTMs) that can directly change nucleosome structure and / or be “read” by chromatin-associated proteins to mediate downstream events. An accurate understanding of histone PTM binding preference is vital to explain normal function and pathogenesis, and has revealed multiple therapeutic opportunities. Such studies most often use histone peptides, even though these cannot represent the full regulatory potential of nucleosome context. Here we apply a range of complementary and easily adoptable biochemical and genomic approaches to interrogate fully defined peptide and nucleosome targets with a diversity of mono or multivalent chromatin readers. In the resulting data, nucleosome context consistently refined reader binding, and multivalent engagement was more often regulatory than simply additive. This included abrogating the binding of the Polycomb group L3MBTL1 MBT to histone tails with lower methyl states (me1 or me2 at H3K4, H3K9, H3K27, H3K36 or H4K20); and confirmation that the CBX7 chromodomain and AT-hook-like motif (CD-ATL) tandem act as a functional unit to confer specificity for H3K27me3. Further, in vitro nucleosome preferences were confirmed by in vivo reader-CUT&RUN genomic mapping. Such data confirms that more representative chromatin substrates provide greater insight to biological mechanism and its disorder in human disease.
Nucleic Acids Research · 2025-09-04 · 1 citations
articleOpen accessHistone H2B contains a highly conserved C-terminal (H2B αC) helix that has been implicated in chromatin interactions and dynamics. The H2B αC helix comprising residues 105-125 is positioned adjacent to a major site of nucleosome interactions called the acidic patch. Despite individual structural studies highlighting interactions between chromatin proteins and the H2B αC helix, the general role of the helix in mediating nucleosome recognition has not been explored. Moreover, many post-translational modifications (PTMs) have been identified within the H2B αC helix, but significant gaps exist in our understanding of their regulatory potential. In this study, we employed nucleosome affinity proteomics using a library of nucleosomes with mutations or PTMs of the H2B αC helix to investigate contributions to nucleosome binding. Our work uncovers new spatial patterns of H2B αC helix engagement across the proteome. We also demonstrate that H2B K120 mono-ubiquitylation (H2B K120ub) within the H2B αC helix broadly disrupts nucleosome binding, phenocopying mutation of the acidic patch, while differentially regulating acidic patch-dependent chromatin functions. In contrast, lysine acetylation results in more subtle position-specific changes, highlighting a more general role of H2B αC helix PTMs in tuning acidic patch recognition.
Nucleosome context regulates chromatin reader preference
Nucleic Acids Research · 2025-10-01 · 2 citations
articleOpen accessChromatin is more than a simple genome packaging system but rather locally distinguished by histone post-translational modifications (PTMs) that can directly change nucleosome structure and/or be "read" by chromatin-associated proteins to mediate downstream events. An accurate understanding of histone PTM binding preference is vital to explain normal function and pathogenesis and has revealed multiple therapeutic opportunities. Such studies most often use histone peptides, though these cannot represent the full regulatory potential of nucleosome context. Here we apply a range of complementary and easily adoptable biochemical and genomic approaches to interrogate fully defined peptide and nucleosome targets with a diversity of mono- or multivalent chromatin readers. In the resulting data, nucleosome context consistently refined reader binding, and multivalent engagement was more often regulatory than simply additive. This included abrogating binding of the Polycomb group malignant brain tumor (MBT) protein L3MBTL1 to lysine methylated histone tails and confirmation that the CBX7 chromodomain and AT-hook-like motif (CD-ATL) tandem act as a functional unit to confer specificity for H3K27me3. These in vitro nucleosome preferences were confirmed by in vivo reader-CUT&RUN genomic mapping. Such data confirms that more representative chromatin substrates provide greater insight into biological mechanism and human disease.
Kryminologia. Teoria, praktyka, metody
Wydawnictwo Naukowe PWN eBooks · 2024-03-01
bookCzyny skierowane przeciwko mieniu, zdrowiu i życiu innych, a także przyrodzie, są stare jak cywilizacja i rozpowszechnione jak ona. Stały się przyczyną powstania norm prawnych, których przekraczanie określamy dziś jako przestępczość. Kryminologia jest nauką, w ramach której opisuje się działania o charakterze przestępczym, poszukuje teorii umożliwiających jej wyjaśnianie i przewidywanie, a co za tym idzie – także przeciwdziałanie przestępczości. Kryminologia jest przy tym dziedziną interdyscyplinarną, która korzysta z dorobku takich nauk, jak prawo, socjologia, pedagogika, psychologia, historia, statystyka, ekonomia, psychiatria czy medycyna. Zespół specjalistów pod kierunkiem Piotra Chomczyńskiego, Przemysława Frąckowiaka i Dagmary Woźniakowskiej opracował kompleksowy podręcznik, przedstawiający rozwój tej dyscypliny, kluczowe teorie wypracowane w jej ramach oraz obecny stan wiedzy na temat przestępczości i przeciwdziałania jej. W pięciu częściach podręcznika czytelnicy znajdą informacje na temat: 1) <b>Teorii kryminologicznych</b> – autorzy i autorki zdefiniowali tu status kryminologii jako nauki, przedstawili rozwój tej dyscypliny oraz wiodące teorie kryminologiczne. 2) <b>Fenomenologii kryminalnej</b> – wybitni specjaliści i specjalistki w swoich dziedzinach przybliżają wiedzę na temat przestępczości w Polsce, przestępczości kobiet, nieletnich, przeciwko mieniu, zdrowiu, życiu, drogowej, gospodarczej, cyberprzestępczości i wielu innych. 3) <b>Wiktymologii</b> – można tu znaleźć kompleksową wiedzę na temat koncepcji wiktymologicznych, wiktymizacji i jej konsekwencji, potrzeb osób pokrzywdzonych przestępstwem i ich udziału w postępowaniu karnym. 4) <b>Zapobieganie przestępczości</b> – autorki i autorzy opisują tu zagadnienia związane z postawami społecznymi wobec przestępczości, profilowaniem, polityką karną i resocjalizacją. 5) <b>Badania kryminologiczne</b> – w tej części została przybliżona metodologia i etyka prowadzenia badań kryminologicznych. Zespół autorski przygotował nowoczesny, kompleksowy, interdyscyplinarny podręcznik. Przystępnie podanej treści towarzyszą: • liczne, unikatowe ilustracje, • bloki rozszerzające, • ciekawostki, • kody QR odsyłające do interesujących źródeł, • materiały dla wykładowców: komplet prezentacji ułatwiających przygotowanie prawie 50 wykładów! A oto liczby: • 3,5 roku pracy • 3 redaktorów naukowych • 35 autorów • 47 rozdziałów • 1000 stron • 47 prezentacji ułatwiających zaplanowanie wykładu We had a dream… Mieliśmy marzenie. Marzenie o podręczniku do kryminologii, jakiego w Polsce jeszcze nie było. Bo przecież podręczniki do tego przedmiotu jak najbardziej mamy: starsze i nowsze, cieńsze i grubsze, bardziej teoretyczne i bardziej praktyczne, mono- i wieloautorskie. Marzył nam się podręcznik nowoczesny, wzorowany na najnowszych trendach przekazywania wiedzy w sposób łatwy, prosty, a przede wszystkim ciekawy. Cóż zatem nowego czy innego mogliśmy zaproponować? Postawiliśmy na kompleksowość, interdyscyplinarność, innowacyjność w treści oraz nowoczesność w formie. Kompleksowość naszego podręcznika polega na tym, że staraliśmy się napisać o wszystkim, co w kryminologii jest ważne, by podróż przez poszczególne zagadnienia była fascynującą przygodą dla naszych Czytelników. Książka składa się z pięciu dużych części. <UL> <LI><a href = "https://images.iformat.pl/48890C2DEB/356E3514-66E8-40EC-BB91-AC38FD0CBF50.epub" download="fragment">Fragment (epub)</a></LI> <LI><a href = "https://images.iformat.pl/48890C2DEB/6C972A81-873F-47C4-AD3D-AA886BC5B6DE.mobi" download="fragment">Fragment (mobi)</a></LI> </UL>
Frequent coauthors
- 142 shared
Peter P. Roller
National Cancer Institute
- 117 shared
Zaneta Nikolovska‐Coleska
University of Michigan–Ann Arbor
- 116 shared
Shaomeng Wang
University of Michigan–Ann Arbor
- 87 shared
Chao‐Yie Yang
University of Michigan–Ann Arbor
- 82 shared
York Tomita
- 79 shared
Jeanne A. Stuckey
University of Michigan–Ann Arbor
- 69 shared
Brian D. Strahl
University of North Carolina at Chapel Hill
- 66 shared
Su Qiu
Hubei University of Chinese Medicine
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