Publications by authors named "Francis S Kim"

5 Publications

  • Page 1 of 1

Non-catalytic ubiquitin binding by A20 prevents psoriatic arthritis-like disease and inflammation.

Nat Immunol 2020 04 16;21(4):422-433. Epub 2020 Mar 16.

Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

A20 is an anti-inflammatory protein that is strongly linked to human disease. Here, we find that mice expressing three distinct targeted mutations of A20's zinc finger 7 (ZF7) ubiquitin-binding motif uniformly developed digit arthritis with features common to psoriatic arthritis, while mice expressing point mutations in A20's OTU or ZF4 motifs did not exhibit this phenotype. Arthritis in A20 mice required T cells and MyD88, was exquisitely sensitive to tumor necrosis factor and interleukin-17A, and persisted in germ-free conditions. A20 cells exhibited prolonged IκB kinase activity that drove exaggerated transcription of late-phase nuclear factor-κB response genes in vitro and in prediseased mouse paws in vivo. In addition, mice expressing double-mutant A20 proteins in A20's ZF4 and ZF7 motifs died perinatally with multi-organ inflammation. Therefore, A20's ZF4 and ZF7 motifs synergistically prevent inflammatory disease in a non-catalytic manner.
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http://dx.doi.org/10.1038/s41590-020-0634-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195210PMC
April 2020

Case 2: Dysphagia to Solid Foods in a 17-month-old Boy.

Pediatr Rev 2017 Oct;38(10):488-489

Division of Pediatric Gastroenterology and Nutrition, Tufts Floating Hospital for Children, Boston, MA.

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http://dx.doi.org/10.1542/pir.2016-0232DOI Listing
October 2017

Experience with corrective surgery for postburn contractures in Mumbai, India.

J Burn Care Res 2012 May-Jun;33(3):e120-6

Division of Burn, Trauma and Critical Care, Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.

Postburn contracture is a source of significant morbidity in India, even though its occurrence can be reduced significantly by comprehensive postburn injury care, including surgical intervention. This study investigates whether limited access to initial medical care after burn injury has been associated with increased contracture formation among lower socioeconomic class patients in Mumbai, India. During a surgical mission in Mumbai, India, patients presenting with functionally debilitating burn contractures and minimal income were surveyed for initial care received immediately after burn injury. The survey consisted of questions regarding the history of burn injury and details of any initial treatment. Demographic data were collected by chart review. Thirty-eight patients from the state of Maharashtra participated in the study (mean age 28.1 years). The most common etiology of burn injury was from kerosene stove blasts (74%), and the most common morbidities were contractures of the neck and upper extremity. On average, time elapsed since the original injury was 2.8 years. Nearly all patients sought initial medical care at hospitals (97%) with the majority receiving only dressing changes for their full-thickness or deep-dermal burns (61%). The most common reason for not seeking out delayed burn reconstruction was perceived cost (65%). Ultimately, 60 operations were performed, of which 9 (15%) developed postsurgical complications. These data suggest that a subset of lower socioeconomic class burn patients in Maharashtra received suboptimal initial intervention. Comprehensive initial therapy after burn injury may provide better outcomes and limit the number of patients requiring delayed reconstruction.
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http://dx.doi.org/10.1097/BCR.0b013e3182335a00DOI Listing
September 2012

Systemic signals regulate ageing and rejuvenation of blood stem cell niches.

Nature 2010 Jan;463(7280):495-500

Department of Stem Cell and Regenerative Biology, Harvard University, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Joslin Diabetes Center, One Joslin Place, Boston, Massachusetts 02115, USA.

Ageing in multicellular organisms typically involves a progressive decline in cell replacement and repair processes, resulting in several physiological deficiencies, including inefficient muscle repair, reduced bone mass, and dysregulation of blood formation (haematopoiesis). Although defects in tissue-resident stem cells clearly contribute to these phenotypes, it is unclear to what extent they reflect stem cell intrinsic alterations or age-related changes in the stem cell supportive microenvironment, or niche. Here, using complementary in vivo and in vitro heterochronic models, we show that age-associated changes in stem cell supportive niche cells deregulate normal haematopoiesis by causing haematopoietic stem cell dysfunction. Furthermore, we find that age-dependent defects in niche cells are systemically regulated and can be reversed by exposure to a young circulation or by neutralization of the conserved longevity regulator, insulin-like growth factor-1, in the marrow microenvironment. Together, these results show a new and critical role for local and systemic factors in signalling age-related haematopoietic decline, and highlight a new model in which blood-borne factors in aged animals act through local niche cells to induce age-dependent disruption of stem cell function.
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http://dx.doi.org/10.1038/nature08749DOI Listing
January 2010

The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells.

Cell Stem Cell 2008 Apr;2(4):380-91

Section on Developmental and Stem Cell Biology, Joslin Diabetes Center, Boston, MA 02115, USA.

EGR1 is a member of the immediate early response transcription factor family and functions in cell growth, development, and stress responses in many tissues. Here we report an additional role for EGR1 in regulating homeostasis of hematopoietic stem cells (HSCs). HSCs normally express Egr1 at high levels, but dramatically downregulate its expression when induced to divide and migrate. Consistent with this finding, mice lacking Egr1 exhibit significant increases in steady-state levels of dividing HSCs in the bone marrow (BM), and a striking spontaneous mobilization of HSCs into the peripheral blood. These data identify EGR1 as a transcriptional regulator of stem cell migration that normally functions to promote HSC quiescence and retention in the niche. The ability of this single factor to regulate both proliferation and mobilization of HSCs suggests that EGR1 commands a genetic program that coordinates stem cell division and migration to maintain appropriate HSC number and function.
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http://dx.doi.org/10.1016/j.stem.2008.01.015DOI Listing
April 2008