About

Taku Kambayashi, M.D., Ph.D., is a Professor of Pathology and Laboratory Medicine at the University of Pennsylvania's Perelman School of Medicine. He serves as an Attending Physician at the Hospital of the University of Pennsylvania for 8 weeks per year and is the Director of the Institute for Immunology Clinical Fellows Training Program at PSOM. Additionally, he is a Program Advisor for the Medical Scientist Training Program at PSOM, a member of the Pathology Residency Steering Committee at HUP, and the Vice Chair of Basic Research in the Department of Pathology at the University of Pennsylvania. His educational background includes a B.S. in Biomedical Engineering from Johns Hopkins University, an M.D. and Ph.D. in Immunology from Emory University. His research expertise focuses on the regulation of T cell responses, signal transduction, skin barrier function, skin commensals, and transgenerational epigenetic inheritance. His specific projects involve studying TSLP-mediated regulation of systemic lipid metabolism by T cells, the regulation of skin barrier function and sebum secretion by Vitamin D3, and the impact of skin and skin microbes on systemic lipid metabolism. He also investigates mouse models of Idiopathic Multicentric Castleman Disease and the regulation of the epigenome of gametes by T cells and microbes, exploring how parental immune factors influence progeny phenotypes. His laboratory personnel include postdoctoral fellows, PhD students, MD/PhD students, and research specialists. His clinical expertise is in transfusion medicine.

Research topics

• Virology
• Biology
• Biochemistry
• Immunology

Selected publications

• The effect of parental T-cell deficiency on offspring response to skin inflammation 9386

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Offspring phenotypes are not only transmitted to the next generation through the DNA code but also through germ cell epigenetic modifications induced by the environment encountered by previous generations. For example, the impact of parental diet and stress on offspring metabolic phenotypes have been well studied. In addition, we have previously shown that the absence of T cells in parents can lead to the epigenetic transmission of certain skin phenotypes across multiple generations. Here, we investigated how parental T cell deficiency influences the offspring skin immune response, despite T cell sufficiency in the offspring. To assess the role of parental T cell deficiency in skin immune response, we employed a mouse model of atopic dermatitis induced by topical application of the Vitamin D3 analog, MC903. Progeny that were generated from a T cell-deficient male crossed to a wildtype female mouse displayed significantly reduced MC903-induced ear inflammation, which correlated with a reduced number of Th17 and Th2 T cells, along with an increased frequency of regulatory T cells in the ear skin. The reduced skin inflammation was observed in both male and female progeny and also in progeny generated from a WT male crossed to a T cell-deficient female. Furthermore, the phenotype persisted even in the F2 generation, independent of their genotype. These data suggest that T cell deficiency in either parent, can non-genetically influence the offspring skin immune response. Funding Sources Supported by NHLBI Hematology Research T32 Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• A lack of commensal microbiota influences the male reproductive tract intergenerationally in mice

  Reproduction · 2025-02-13 · 3 citations

  articleOpen access

  In brief: Germ-free mice display epididymal transcriptomic changes that were also evident in their conventionalized male offspring and mice lacking T and B cells. This paper demonstrates the role of microbiota and immune cells in the epididymis. Abstract: The microbiome encompasses the array of microorganisms inhabiting various niches in the body and is necessary for numerous physiological processes, including normal metabolism and a functioning immune system. Not only does the absence of a microbiome in mice impact the exposed animals but also inherited phenotypes in successive generations of progeny, suggesting that the absence of a microbiome impacts the germline and gametes. Indeed, recent research has identified a role of the gut microbiome in contributing to male fertility, in both healthy and disease states. While this link is beginning to be established, the impact of the microbiome on the male reproductive tract remains understudied. Here, we utilized a germ-free mouse model to examine the influence of the absence of microbes on the male reproductive tract. In contrast to mice with an established microbiome, germ-free mice display decreased testicular weight and the prevalence of an epididymitis-like inflammation phenotype. These histopathological changes are accompanied by transcriptomic dysregulation in the reproductive tract of germ-free mice, particularly in the cauda epididymis. Moreover, these transcriptomic changes are transmitted to the next generation with high correlation of gene expression in the cauda epididymis between germ-free mice and their conventionalized (microbiome-restored) male offspring, when compared to control mice. Ultimately, our findings identify the reproductive sequalae of males without a functional microbiome and additionally in their conventionalized offspring, suggesting that the paternal microbiota is an underappreciated contributor to male reproductive function.

  PublisherDOI

• A patient-derived CABIN1 mutation recapitulates features of idiopathic multicentric Castleman disease in a mouse model

  Blood Advances · 2025-08-14 · 1 citations

  articleOpen access
  PublisherOA PDFDOI

• Acetyl-CoA synthesis in the skin is a key determinant of systemic lipid homeostasis

  Cell Reports · 2025-02-01 · 5 citations

  articleOpen access

  ATP-citrate lyase (ACLY) generates cytosolic acetyl-coenzyme A (acetyl-CoA) for lipid synthesis and is a promising therapeutic target in diseases with altered lipid metabolism. Here, we developed inducible whole-body Acly-knockout mice to determine the requirement for ACLY in normal tissue functions, uncovering its crucial role in skin homeostasis. ACLY-deficient skin upregulates the acetyl-CoA synthetase ACSS2; deletion of both Acly and Acss2 from the skin exacerbates skin abnormalities, with differential effects on two major lipid-producing skin compartments. While the epidermis is depleted of barrier lipids, the sebaceous glands increase production of sebum, supplied at least in part by circulating fatty acids and coinciding with adipose lipolysis and fat depletion. Dietary fat supplementation further boosts sebum production and partially rescues both the lipoatrophy and the aberrant skin phenotypes. The data establish a critical role for cytosolic acetyl-CoA synthesis in maintaining skin barrier integrity and highlight the skin as a key organ in systemic lipid regulation.

  PublisherDOI

• The microbiota and T cells non-genetically modulate inherited phenotypes transgenerationally

  Cell Reports · 2024-04-01 · 9 citations

  articleOpen accessSenior authorCorresponding

  The host-microbiota relationship has evolved to shape mammalian physiology, including immunity, metabolism, and development. Germ-free models are widely used to study microbial effects on host processes such as immunity. Here, we find that both germ-free and T cell-deficient mice exhibit a robust sebum secretion defect persisting across multiple generations despite microbial colonization and T cell repletion. These phenotypes are inherited by progeny conceived during in vitro fertilization using germ-free sperm and eggs, demonstrating that non-genetic information in the gametes is required for microbial-dependent phenotypic transmission. Accordingly, gene expression in early embryos derived from gametes from germ-free or T cell-deficient mice is strikingly and similarly altered. Our findings demonstrate that microbial- and immune-dependent regulation of non-genetic information in the gametes can transmit inherited phenotypes transgenerationally in mice. This mechanism could rapidly generate phenotypic diversity to enhance host adaptation to environmental perturbations.

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• Diacylglycerol kinase zeta deficiency attenuates papain-induced type 2 airway inflammation

  Cellular Immunology · 2023-10-29 · 2 citations

  articleSenior authorCorresponding
  PublisherDOI

• Thymic stromal lymphopoietin induces IL-4/IL-13 from T cells to promote sebum secretion and adipose loss

  Journal of Allergy and Clinical Immunology · 2023-12-28 · 9 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Immature natural killer cells promote progression of triple-negative breast cancer

  Science Translational Medicine · 2023-03-08 · 76 citations

  articleOpen access

  Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3 high CD11b − CD27 − immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell–mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti–programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56 bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC.

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• Novel Combination Treatment for Melanoma: FLASH Radiotherapy and Immunotherapy Delivered by a Radiopaque and Radiation Responsive Hydrogel

  Chemistry of Materials · 2023-11-14 · 12 citations

  articleOpen access

  Immunotherapies have become the standard treatment for melanoma. To further improve patient responses, combinations of immunotherapies and radiotherapy (RT) are being studied, since radiotherapies can potentially provide additional immune stimulation, in addition to direct antitumor effects. FLASH-RT is a novel, ultrahigh dose rate, radiation delivery approach, with the potential of at least equivalent tumor control efficacy and reduced damage to healthy tissue. However, the effects of combining FLASH-RT and immunotherapy have not been extensively studied in melanoma. Toll-like receptor (TLR) agonists, such as imiquimod (IMQ), are potent immunostimulatory agents, although their utility is limited due to poor solubility and systemic side effects. We therefore developed a novel combination therapy for melanoma consisting of IMQ delivered to the tumor via a radiopaque and radiation responsive hydrogel combined with FLASH-RT. We found that FLASH was able to effectively stimulate IMQ release from the hydrogel. In addition, we found that the combination of FLASH and released IMQ resulted in synergistic melanoma cell killing in vitro. The combination therapy reduced tumor growth compared to controls, enhanced survival, and resulted in remarkable enhancements in certain tumor cytokine levels. CT imaging allowed the hydrogel to be monitored in vivo. In addition, no adverse effects of the treatment were observed. Overall, this IMQ-gel and FLASH-RT combination may have potential as an improved treatment for melanoma and indicates that the interactions of FLASH-RT and TLR agonists merit further study.

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• OA5‐AM23‐MN‐36 | Red Cell Exchange for Rapid Leukoreduction in Adults with Hyperleukocytosis and Leukostasis

  Transfusion · 2023-10-01

  articleOpen access

  Hyperleukocytosis with leukostasis is a complication of acute leukemias that is associated with significant morbidity. While cytoreductive chemotherapy can reduce the white blood cell count (WBC) and improve symptoms of leukostasis, therapeutic leukocytapheresis (TLP) can rapidly reduce WBC when needed. Notably, some patients fail to achieve the desired WBC reduction with TLP. Thus, we hypothesized that some leukemic blasts are difficult to separate from red cells by centrifugation and that red cell exchange (RCE) may more effectively remove these blasts. We began using RCE to treat hyperleukocytosis with leukostasis in patients with suboptimal WBC reduction from TLP. RCE was also used to correct anemia in a subset of these patients. Overtime, RCE became a first line therapy in several cases where we predicted better outcomes with RCE. We retrospectively examined the charts of adults with leukostasis who underwent a leukoreduction procedure at our institution from 2017 to 2023. Specifically, we examined the charts of 60 patients who received TLP alone, 10 who received RCE after a suboptimal response to TLP, and 5 who received RCE alone. Outcomes examined were changes in WBC, hematocrit, hemoglobin, INR, and 30-day survival. Demographics and starting WBCs of the groups were similar; however, the patients that underwent RCE were enriched for monocytic leukemias and were more anemic. In a subset of patients who had a suboptimal response to TLP, we performed RCE and achieved a ~2-fold greater WBC reduction (Figure A). We saw a similar WBC reduction in patients treated with first line RCE. A striking advantage of RCE was our ability to simultaneously increase hematocrit without concern for increasing blood viscosity. Moreover, the processing time was twice as long for TLP. There was no difference in 30-day survival between patients who received TLP or RCE. Figure A: WBC reduction with TLP and RCE. RCE, red cell exchange; TLP, therapeutic leukocytapheresis; WBC, white blood cell count.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R01HL107589

  NIH · $2.0M · 2016

• NIH Grant R21AI117282

  NIH · $440k · 2017

• Diacylglycerol kinase in airway smooth muscle functions

  NIH · $2.8M · 2019–2025

• The Role of Post-translational Modifier PRMT5 in Regulatory T cell Development and Function

  NIH · $443k · 2018–2021

• Novel strategies for regulatory T cell expansion

  NIH · $3.6M · 2012–2022

Frequent coauthors

• Hans‐Gustaf Ljunggren

  Karolinska Institutet

  36 shared

• Gary A. Koretzky

  Weill Cornell Medicine

  35 shared

• Mariko Okumura

  University of Pennsylvania

  22 shared

• Marina Ziche

  University of Siena

  17 shared

• Daria Donati

  Trenitalia (Italy)

  17 shared

• Maria Teresa Bejarano

  University of Castilla-La Mancha

  17 shared

• Harris J. Granger

  17 shared

• Sandra Donnini

  University of Siena

  17 shared

Labs

• Kambayashi LabPI