Research

Academic Publications

Early Clostridium difficile infection during allogeneic hematopoietic stem cell transplantation.
Kinnebrew MA, Lee YJ, Jenq RR, Lipuma L, Littmann ER, Gobourne A, No D, vanden Brink M, Pamer EG, Taur Y. PLoS One. 2014 Mar 24;9(3)

Infection with the bacterium Clostridium difficile, commonly known as C. Diff, is the most common cause of diarrhea in hospitalized patients. In this study, we analyzed fecal samples of patients receiving treatment for blood cancers to determine how many of these patients get infected with C. Diff during the course of their treatment, when these infections occur, and how severe the infections are.

Quantitative assessment of T cell repertoire recovery after hematopoietic stem cell transplantation.
van Heijst JW, Ceberio I, Lipuma L, Samilo DW, Wasilewski GD, Gonzales AM, Nieves JL, van den Brink MR, Perales MA, Pamer EG. Nat Med. 2013 Mar;19(3):372-7.

The human body can defend itself against a broad spectrum of disease-causing microbes. Part of the reason our immune inventory is so vast is because our T cells can recognize roughly 25 million different foreign molecules. But treating certain blood cancers requires killing off all of a person’s T cells and replenishing them with cells from someone else. When patients recover from this procedure, can their new T cells learn to recognize all of those foreign invaders? Or are their immune systems forever compromised? In this study, we show that many patients don’t recover their original immune inventory even a year after such a procedure.

Intestinal microbiota containing Barnesiella species cures vancomycin-resistant Enterococcus faecium colonization.
Ubeda C, Bucci V, Caballero S, Djukovic A, Toussaint NC, Equinda M, Lipuma L, Ling L, Gobourne A, No D, Taur Y, Jenq RR, van den Brink MR, Xavier JB, Pamer EG. Infect Immun. 2013 Mar;81(3):965-73.

The bacteria that reside in our guts do us the favor of preventing harmful microbes from setting up shop and causing an infection, but we lose this protection  when we take antibiotics. But what happens if we seed our intestines with helpful gut bacteria after a course of antibiotics? Can they still protect us? Or even cure an existing infection? In this study, we show that replacing the gut flora lost during antibiotic treatment with one kind of helpful bacteria can cure mice of potentially lethal gut infections.

Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice.
Ubeda C, Lipuma L, Gobourne A, Viale A, Leiner I, Equinda M, Khanin R, Pamer EG. J Exp Med. 2012 Jul 30;209(8):1445-56.

The immune system mediates what kind of microbes can take up residence in our intestines. So do people with certain kinds of immune system deficiencies have different microbes in their guts than people with healthy immune systems? In this study, we show that mice lacking certain immune system signaling molecules  develop microbial communities in their guts similar to their littermates that have no immune defects. This suggests those signaling molecules aren’t essential for creating a healthy gut flora.

Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. 
Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Clin Infect Dis. 2012
Oct;55(7):905-14.

Hospital patients with compromised immune systems take large amounts of antibiotics to prevent infections during their treatment. But those antibiotics can disrupt the normal gut flora. In this study, we show that antibiotics deplete native gut microbes in patients receiving treatment for certain blood cancers. This allows harmful bacteria to dominate the intestines and in some cases, enter the bloodstream, which can be fatal.

Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis.
Scher JU, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A, Lipuma L, Attur M, Pillinger MH, Weissmann G, Littman DR, Pamer EG, Bretz WA, Abramson SB. Arthritis Rheum. 2012 Oct;64(10):3083-94.

Rheumatoid arthritis is a autoimmune disease whose onset doctors don’t fully understand. But doctors do know that autoimmunity is often regulated by crosstalk between white blood cells and the microbes that inhabit our bodies. In this study, we compare the oral microbes of patients with rheumatoid arthritis to those of normal patients to see if specific oral microbes are associated with development of rheumatoid arthritis symptoms.

Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation.
Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, Gobourne A, Lipuma L, Young LF, Smith OM, Ghosh A, Hanash AM, Goldberg JD, Aoyama K, Blazar BR, Pamer EG, van den Brink MR.  J Exp Med. 2012 May 7;209(5):903-11.

Researchers have recently come to understand that there is a link between inflammation in the gut and the microbes that reside there. In this study, we show that patients who undergo treatment for certain blood cancers experience dramatic changes in the composition of their gut microbes. We find those shifts can exacerbate or ameliorate post-treatment gut inflammation, a major factor in determining the success of the treatment.

Profound alterations of intestinal microbiota following a single dose of clindamycin results in sustained susceptibility to Clostridium difficile-induced colitis.
Buffie CG, Jarchum I, Equinda M, Lipuma L, Gobourne A, Viale A, Ubeda C, Xavier J, Pamer EG. PInfect Immun. 2012 Jan;80(1):62-73.

The bacteria that reside in our guts—our intestinal microbiota—can be thought of as a diverse, complex ecosystem. We know that antibiotics can disrupt this ecosystem, but how does that affect how susceptible we are to infection? In this study, we show that a single dose of clindamycin profoundly alters the gut microbial ecosystem and increases a person’s susceptibility to C. Diff infection.

Bone marrow mesenchymal stem and progenitor cells induce monocyte emigration in response to circulating toll-like receptor ligands. 
Shi C, Jia T, Mendez-Ferrer S, Hohl TM, Serbina NV, Lipuma L, Leiner I, Li MO, Frenette PS, Pamer EG. Immunity. 2011 Apr 22;34(4):590-601.

How does the body initiate an immune response when it senses the presence of a harmful microbe? In this study, we show that bacterial proteins circulating in the bloodstream during an infection stimulate a certain kind of stem cells in the bone marrow to produce a chemical that jumpstarts the immune system reaction to the infection.

Toll-like receptor 5 stimulation protects mice from acute Clostridium difficile colitis. 
Jarchum I, Liu M, Lipuma L, Pamer EG. Infect Immun. 2011 Apr;79(4):1498-503.

Toll-like receptors are proteins found in almost all animals that activate the immune system and maintain the integrity of the intestinal lining. In this study, we show that artificially stimulating one kind of toll-like receptor in mice protects those mice from C. Diff infection. This shows that doctors could potentially use artificial stimulation as a strategy to prevent gut inflammation caused by C. Diff in humans.

Inflammatory monocytes facilitate adaptive CD4 T cell responses during respiratory fungal infection.
Hohl TM, Rivera A, Lipuma L, Gallegos A, Shi C, Mack M, Pamer EG. Cell Host Microbe. 2009 Nov 19;6(5):470-81.

How do the cells of the innate and adaptive immune system interact during a fungal infection? In this study, we show that innate immune cells carry fungal proteins to the lymph nodes, prime adaptive immune cells and facilitate clearance of the infection.

Essential role for neutrophils but not alveolar macrophages at early time points following Aspergillus fumigatus infection.
Mircescu MM, Lipuma L, van Rooijen N, Pamer EG, Hohl TM. J Infect Dis. 2009 Aug 15;200(4):647-56.

What cells are more important in controlling fungal growth right after an infection: neutrophils or macrophages? In this study, we show that neutrophils are essential for preventing fungal growth immediately following infection, but alveolar macrophages are not.

Aberrant tissue localization of fungus-specific CD4+ T cells in IL-10-deficient mice.
Rivera A, Collins N, Stephan MT, Lipuma L, Leiner I, Pamer EG. J Immunol. 2009 Jul 1;183(1):631-41.

IL-10 is a protein that acts as an essential immune regulator in the intestinal tract, and mice who can’t produce IL-10 often develop intestinal inflammation. In this study, we show intestinal inflammation caused by IL-10 deficiency causes helper T cells to migrate to the gut to control the inflammation—even when there is an infection in another area of the body.