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Research description

Improving HIV therapy by chromatin modulation

35 million people are currently living with HIV. Work in our group aims of improve HIV therapy and eradicating the virus by reducing and possibly eliminating the reservoir of latently infected cells. The reservoir is challenging to study as the latently infected cells are rare (1 in a million CD4+ cells) and portions of the reservoir contain no viral proteins at all. The reservoir can be eliminated either by activating the provirus by an latency reversal agent (LRA) followed by destruction of the cell (“shock and kill”) (Fig 1), by permanent inactivating the provirus (“lock-and-block”), or by a combination of the two as to target distinct subsets of the reservoir 

Our main focus is controlling the chromatin composition and transcriptional state of the provirus. We have developed unique single-molecule techniques to study and interfere with the viral life-cycle in HIV+ patients. 

 

Lines of research

1. Identify and quantitate the reservoir of latently infected cells in HIV+ patients.

2. Validate a transcription elongation complex as a drug target to activate HIV.

3. Find new cellular protein targets for HIV latency reversal agents.

 

 

 

Academic honours, awards and prizes

Publications

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Publications

Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells
Battivelli E, Dahabieh Ms, Abdel-mohsen M, Svensson Jp, Tojal Da Silva I, Cohn Lb, et al
eLife 2018;7():-

The mTOR Complex Controls HIV Latency
Besnard E, Hakre S, Kampmann M, Lim Hw, Hosmane Nn, Martin A, et al
Cell host & microbe 2016;20(6):785-797

A nucleosome turnover map reveals that the stability of histone H4 Lys20 methylation depends on histone recycling in transcribed chromatin
Svensson Jp, Shukla M, Menendez-benito V, Norman-axelsson U, Audergon P, Sinha I, et al
Genome research 2015;25(6):872-83

PARP1- and CTCF-Mediated Interactions between Active and Repressed Chromatin at the Lamina Promote Oscillating Transcription
Zhao H, Sifakis Eg, Sumida N, Millán-ariño L, Scholz Ba, Svensson Jp, et al
Molecular cell 2015;59(6):984-97

The Paf1 complex factors Leo1 and Paf1 promote local histone turnover to modulate chromatin states in fission yeast
Sadeghi L, Prasad P, Ekwall K, Cohen A, Svensson Jp
EMBO reports 2015;16(12):1673-87

Centromeric histone H2B monoubiquitination promotes noncoding transcription and chromatin integrity
Sadeghi L, Siggens L, Svensson Jp, Ekwall K
Nature structural & molecular biology 2014;21(3):236-43

Epigenetic activation and inactivation of centromeres
Svensson Jp, Ekwall K
Epigenomics 2014;6(5):451-4

Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure
Svensson Jp, Quirós Pesudo L, Mcree Sk, Adeleye Y, Carmichael P, Samson Ld
PloS one 2013;8(9):e73736-

Microfluidic genome-wide profiling of intrinsic electrical properties in Saccharomyces cerevisiae
Vahey Md, Pesudo Lq, Svensson Jp, Samson Ld, Voldman J
LAB ON A CHIP 2013;13(14):2754-63

CHD1 remodelers regulate nucleosome spacing in vitro and align nucleosomal arrays over gene coding regions in S. pombe
Pointner J, Persson J, Prasad P, Norman-axelsson U, Stralfors A, Khorosjutina O, et al
EMBO JOURNAL 2012;31(23):4388-403

Factors That Promote H3 Chromatin Integrity during Transcription Prevent Promiscuous Deposition of CENP-A(Cnp1) in Fission Yeast
Choi Es, Stralfors A, Catania S, Castillo Ag, Svensson Jp, Pidoux Al, et al
PLOS GENETICS 2012;8(9):e1002985-

Hierarchical Modularity and the Evolution of Genetic Interactomes across Species
Ryan Cj, Roguev A, Patrick K, Xu Jw, Jahari H, Tong Zt, et al
MOLECULAR CELL 2012;46(5):691-704

Identification of Novel Human Damage Response Proteins Targeted through Yeast Orthology
Svensson Jp, Fry Rc, Wang Em, Somoza La, Samson Ld
PLOS ONE 2012;7(5):e37368-

Genomic phenotyping of the essential and non-essential yeast genome detects novel pathways for alkylation resistance
Svensson Jp, Pesudo Lq, Fry Rc, Adeleye Ya, Carmichael P, Samson Ld
BMC SYSTEMS BIOLOGY 2011;:157-

Podbat: A Novel Genomic Tool Reveals Swr1-Independent H2A.Z Incorporation at Gene Coding Sequences through Epigenetic Meta-Analysis
Sadeghi L, Bonilla C, Stralfors A, Ekwall K, Svensson Jp
PLOS COMPUTATIONAL BIOLOGY 2011;7(8):e1002163-

Analyzing genetic interactions to elucidate DNA damage responsive networks and toxicity mechanisms of environmental agents in yeast
Quiros L, Svensson P, Wang E, Fry R, Samson Ld
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2008;49(7):578-578

Genomic predictors of interindividual differences in response to DNA damaging agents
Fry Rc, Svensson Jp, Valiathan C, Wang E, Hogan Bj, Bhattacharya S, et al
GENES & DEVELOPMENT 2008;22(19):2621-6

Identifying novel human damage response proteins based on yeast orthology
Svensson P, Rebecca Fr, Samson Ld
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2008;49(7):578-578

Scientists find genes to predict chemotherapy outcome
Fry Rc, Svensson Jp, Valiathan C
PERSONALIZED MEDICINE 2008;5(6):561-561

Activation of inflammation/NF-kappa B signaling in infants born to arsenic-exposed mothers
Fry Rc, Navasumrit P, Valiathan C, Svensson Jp, Hogan Bj, Luo M, et al
PLOS GENETICS 2007;3(11):2180-2189

A portrait of cisplatin-induced transcriptional changes in mouse embryonic stem cells reveals a dominant p53-like response
Kruse Jjcm, Svensson Jp, Huigsloot M, Giphart-gassler M, Schoonen Wgej, Polman Jem, et al
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 2007;617(1-2):58-70

Transcriptional Networks in S-cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates
Rusyn I, Fry Rc, Begley Tj, Klapacz J, Svensson Jp, Ambrose M, et al
PLOS ONE 2007;2(11):e1252-

Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation
Van Bezooijen Rl, Svensson Jp, Eefting D, Visser A, Van Der Horst G, Karperien M, et al
JOURNAL OF BONE AND MINERAL RESEARCH 2007;22(1):19-28

Analysis of gene expression using gene sets discriminates cancer patients with and without late radiation toxicity
Svensson Jp, Stalpers Lja, Esveldt-van Lange Ree, Franken Nap, Haveman J, Klein B, et al
PLOS MEDICINE 2006;3(10):1904-1914

Dissecting systems-wide data using mixture models: application to identify affected cellular processes
Svensson Jp, De Menezes Rx, Turesson I, Giphart-gassler M, Vrieling H
BMC BIOINFORMATICS 2005;:177-

Distinct nuclear gene expression profiles in cells with mtDNA depletion and homoplasmic A3243G mutation
Tafrechi Rsj, Svensson Pj, Janssen Gmc, Szuhai K, Maassen Ja, Raap Ak
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS 2005;578(1-2):43-52

Microarray analysis of gene expression profiles of cardiac myocytes and fibroblasts after mechanical stress, ionising or ultraviolet radiation
Boerma M, Van Der Wees Cgc, Vrieling H, Svensson Jp, Wondergem J, Van Der Laarse A, et al
BMC GENOMICS 2005;:6-

Mitochondrial DNA mutations distinctively alter nuclear gene expression
Jahangir R, Svensson P, Janssen G, Szuhai K, Maassen Ja, Raap A
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS 2004;:82-82

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