Genome organization and dynamics

across scales

Research

We study the organizing principles of the genome and how these principles regulate cell identity and developmental switches

Model for genome packaging. DNA is wrapped around nucleosomes, the fundamental unit of chromatin. The 10-nm fiber of nucleosomes is a fluid polymer that organizes through weak and multivalent interactions. Nucleosome conformational dynamics, post-tr…

Model for genome packaging. DNA is wrapped around nucleosomes, the fundamental unit of chromatin. The 10-nm fiber of nucleosomes is a fluid polymer that organizes through weak and multivalent interactions. Nucleosome conformational dynamics, post-translational modifications and chromatin-binding proteins regulate such interactions and chromatin folding into phase-separated condensates.

 

Eukaryotic DNA is wrapped around nucleosomes, which form long chains of chromatin that are further folded into three-dimensional assemblies. The architecture of these assemblies is crucial for determining cell identity and for proper cellular functions. Recent findings have challenged classical models of hierarchical chromatin organization at different levels. At the meso-scale level, we appreciate that chromatin folding is based on structures that are less ordered and less discrete than previously proposed and that phase separation can contribute to functional organization of the genome. At the nucleosome level, we realized that nucleosomes are not rigid like Lego blocks, but they can undergo dynamic conformational changes that regulate chromatin folding.

We are interested in dissecting the links among atomic-scale chromatin dynamics, higher-level chromatin structure, and biological functions.

We combine Biochemistry and Biophysical methods such as NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology, and Genetics to explore genome organization across length and time scales and understand how cells leverage the diverse biophysical properties of chromatin to regulate genome function.

We have a special focus on:

  • chromatin atomic-scale dynamics and nucleosome conformational changes

  • chromatin meso-scale organization and phase separation

Publications

 

Phase Separation in Biology and Disease: Current Perspectives and Open Questions. Boeynaems  S, Chong S, Gsponer J, Holt  L, Milovanovic  D, Mitrea  DM, Mueller-Cajar  O, Portz  B, Reilly  JF, Reinkemeier  CD, Sabari  BR, Sanulli  S, Shorter  J, Sontag  E, Strader  L, Stachowiak  J, Weber  SC, White  M, Zhang  H, Zweckstetter  M, Elbaum-Garfinkle  S, Kriwacki  R. Current Perspectives and Open Questions. J Mol Biol. 2023 Mar 1;435(5):167971. PMID: 36690068

Generation and Biochemical Characterization of Phase-Separated Droplets Formed by Nucleic Acid Binding Proteins: Using HP1 as a Model System. Sanulli S and Narlikar GJ. Curr Protoc 2021 May;1(5):e109.PMID: 33950570

Biophysical Properties of HP1-Mediated Heterochromatin.
Sanulli S,
Gross JD, Narlikar GJ. Cold Spring Harb Symp Quant Biol. 2020. PMID: 32493764

Liquid-like interactions in heterochromatin: Implications for mechanism and regulation.
Sanulli S, J Narlikar G. Curr Opin Cell Biol. 2020. PMID: 32434105

HP1 reshapes nucleosome core to promote phase separation of heterochromatin.
Sanulli S, Trnka MJ, Dhamarajan V, Tibble RW, Pascal BD, Burlingame AL, Griffin PR, Gross JD, Narlikar GJ. Nature 2019. PMID: 31618757

Biochemical Basis for Distinct Roles of the Heterochromatin Proteins Swi6 and Chp2.
Isaac RS, Sanulli S, Tibble R, Hornsby M, Ravalin M, Craik CS, Gross JD, Narlikar GJ. J Mol Biol. 2017. PMID: 28942089

Jarid2 Methylation via the PRC2 Complex Regulates H3K27me3 Deposition during Cell Differentiation.
Sanulli S, Justin N, Teissandier A, Ancelin K, Portoso M, Caron M, Michaud A, Lombard B, da Rocha ST, Offer J, Loew D, Servant N, Wassef M, Burlina F, Gamblin SJ, Heard E, Margueron R. Mol Cell. 2015. PMID: 25620564

Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.
da Rocha ST, Boeva V, Escamilla-Del-Arenal M, Ancelin K, Granier C, Matias NR, Sanulli S, Chow J, Schulz E, Picard C, Kaneko S, Helin K, Reinberg D, Stewart AF, Wutz A, Margueron R, Heard E. Mol Cell. 2014. PMID: 24462204

Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication.
Rolando M, Sanulli S, Rusniok C, Gomez-Valero L, Bertholet C, Sahr T, Margueron R, Buchrieser C. Cell Host Microbe 2013. PMID: 23601102

About us

 
 
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Serena Sanulli

She/her/ hers Assistant Professor
Chan Zuckerberg Biohub Investigator

Serena obtained her PhD in 2013 from the Université Pierre and Marie Curie in France, studying chromatin changes in development with Raphaël Margueron. She moved to San Francisco in 2014 for a post-doctoral training at UCSF with Geeta Narlikar and John Gross, where she applied biophysical methods to study chromatin structure and organization.

In January 2021 she joined the Department of Genetics at Stanford University as an Assistant Professor and she is a Chan Zuckerberg Biohub Investigator. In 2022, Serena was named Searle Scholar and received the NIH Innovator Award.

ssanulli[at]stanford[dot]edu

 
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Ali Wilkening

She/her/hers Graduate Student Developmental Biology

Ali is a PhD student in Stanford’s Developmental Biology Department broadly interested in understanding the molecular mechanisms driving evolutionary diversification. She received a BA in Biology with an emphasis in Computational Genomics from Washington University in St. Louis in 2020. As an undergraduate, she first worked with Eric Haden at Boise State University where she helped characterize the impact of a sagebrush diet on the microbiome of mule deer. She then worked with Ting Wang at WashU where she uncovered transcription factors that determine iridophore cell fate in zebrafish. Ali is excited to learn more about how histone core variants can impact chromatin architecture, gene regulation, and, ultimately, morphology. Outside of the lab, she enjoys knitting, dancing and riding her horse, Chewbacca.

alicianw[at]stanford[dot]edu

 
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James Medwid

Research Associate

James graduated from the University of California, San Diego with a BS in Biology with a specialization in Bioinformatics, as well as a minor in Psychology. During his time in undergrad, he worked at Mirati Therapeutics, helping develop targeted small-molecule cancer therapies. With a passion for knowledge and understanding, he is excited to dive deeper into the mechanisms underlying chromatin organization and the implications of these structural changes on development and disease. In his free time, he likes to produce and DJ electronic music, go backpacking, and try out new cooking recipes.

jmedwid[at]stanford[dot]edu

 

Arianna Silva-Torres

She/her/hers

Graduate Student Cancer Biology

Arianna is a PhD student in Stanford’s Cancer Biology program. She is broadly interested in how phase separation may drive oncogenesis in solid tumors, and how such phase separation can be exploited by therapeutics leading to better, more efficient therapies for cancers that have a poor outcome with current treatments. Arianna obtained a BS in molecular biology from UC San Diego in 2018. After graduating, she worked at City of Hope in Dr. Shi’s lab to develop a stem cell based therapy for Canavan Disease, and then worked at Bristol Myers Squibb in their protein homeostasis group to find new targets for CELMoDs and IMiDs. Outside of the lab, she enjoys weightlifting, hiking, and reading.

asilvato[at]stanford[dot]edu

 

Monika Priyadarshini

Postdoctoral Fellow

Monika obtained her PhD from the Biological and Environmental Science Division at King Abdullah University for Science and Technology (KAUST, Saudi Arabia) in 2021. She worked with Christian Frøkjær-Jensen to study epigenetic regulation of germline genes and transgenerational inheritance of silencing in C. elegans . She is passionate about epigenetics, synthetic and molecular biology, and protein biochemistry. She is interested in deciphering the “rules” for genome organization and dissecting the molecular and structural changes occurring in chromatin.

mnk[at]stanford[dot]edu

 

Matthew Wong

He/him/his

Postdoctoral Fellow

Matthew received his PhD from the University of Ottawa in 2022 for his research with Dr. Jeffrey Dilworth examining the functions of the epigenetic regulators in muscle growth and the onset of muscular dystrophy. He has a profound interest in cell biology, epigenetics and bioinformatics. He is curious to understand how phase separation would affect the protein interactome, gene expression and chromatin organization inside the cell, and how these changes are essential for normal cellular functions and developmental stages. Outside the lab, he enjoys cooking and watching movies.

matmkw[at]stanford[dot]edu

 

Aoon Rizvi

He/him/his

Postdoctoral Fellow

 Aoon is interested in phase separation of biomacromolecules and what unique structures can emerge during this process. During his PhD, Aoon worked on block copolymer self-assembly in the Patterson lab at UC Irvine. He did his  BS in Chemistry from University of Illinois at Urbana Champaign. Aoon is passionate about teaching and mentorship and hope to grow as scientific leader.  Aside from science, he loves to cook and explore the world!

aoonr[at]stanford[dot]edu

Aishwarya Arya

She/her/hers

Research Associate and Lab manager

Aishwarya is a dedicated full-time research professional, holding a Masters in Biotechnology from Texas A&M University, where she spent over five years contributing to Research and Development efforts at various labs. Following her time at the university, she gained further experience by working for more than two years at a Bio-pharma company. Her recent focus has been on mRNA-based therapeutics and the discovery of innovative flu and COVID vaccines. Recently, she successfully completed her MBA, which complements her scientific background and fuels her passion for exploring the junction of disease biology and practical implementation in real-world scenarios. Beyond her work, Aishwarya finds joy in gardening, traveling, blog writing, and staying active through swimming.

Ezekiel Delgado

He/him/his

Graduate Student Genetics

Ezekiel is a PhD student in Stanford’s Genetics Department. He is interested in better understanding how the genome is organized and developing new methods to explore gene regulation. Ezekiel obtained a BS in Molecular, Cell, and Developmental Biology from UCLA in 2023. As an undergraduate he researched the molecular mechanisms regulating thermogenesis in brown adipocytes in the lab of Dr. Claudio Villanueva. Outside of the lab he enjoys photography and trying new coffee shops.

edelgado[at]stanford[dot]edu

Ashfeen Nawar

Research Associate

ashnawar[at]stanford[dot]edu

Soua Lee

Administrative Assistant

soua[at]stanford[dot]edu

Past members

Siran Zhang Stanford Summer School Student - Summer 2023

Amélie Wileveau Master Student - Summer 2023

Colette Benko Rotation Student - Winter 2022-2023

Raeline Valbuena Graduate Student - 2021-2022

Alvina Adimoelja Rotation Student - Winter 2021-2022

Akshi Goyal Lab manager - 2020-2022

Darren Lam Rotation Student - Fall 2021-2022

Micah Olivas Rotation Student - Winter 2020-2021

Join the team!

We are recruiting highly motivated graduate students and post-doctoral fellows.

Graduate students should apply to one of the Stanford graduate programs.

Postdoctoral fellows should contact Serena with a CV, research interest, and three references.

We welcome trainees with different background

excited to build an interdisciplinary and curiosity-driven team that values diversity, equity, and inclusion.

If you are interested in joining us, contact Serena ssanulli(at)stanford(dot)edu

Land Acknowledgement

We recognize that Stanford sits on the ancestral land of the Muwekma Ohlone Tribe. This land was and continues to be of great importance to the Ohlone people. Consistent with our values of community and inclusion, we have a responsibility to acknowledge, honor and make visible the university’s relationship to Native peoples.

Visit Us

Department of Genetics
Stanford University
Biomedical Innovation Building
240 Pasteur Dr, Palo Alto, CA 94304