Helmuth Goepfert, MD, Oral History Interview, August 28, 2012

Major Topics Covered: Biomedical publishing; ethics Biomedical/clinical education, educational publications The Physicians Network MD Anderson presidents MD Anderson culturehttps://openworks.mdanderson.org/mchv_interviewsessions/1212/thumbnail.jp

Helmuth Goepfert, MD, Oral History Interview, August 27, 2012

Major Topics Covered: Personal and educational background Head and Neck oncology: evolution of; patient experiences of; special challenges History of head and neck surgery; evolution into multi-disciplinary team collaboration Section of Head and Neck Surgery Research: combining surgery with chemotherapy and radiation therapy to preserve laryngeal function Interdisciplinary care for head and neck cancers at MD Andersonhttps://openworks.mdanderson.org/mchv_interviewsessions/1211/thumbnail.jp

Menstrual Blood as a Potential Source of Endometrial Derived CD3+ T Cells

Studies of T cell-mediated immunity in the human female genital tract have been problematic due to difficulties associated with the collection of mucosal samples. Consequently, most studies rely on biopsies from the lower female genital tract or remnant tissue from hysterectomies. Availability of samples from healthy women is limited, as most studies are carried out in women with underlying pathologies. Menstruation is the cyclical sloughing off of endometrial tissue, and thus it should be a source of endometrial cells without the need for a biopsy. We isolated and phenotyped T cells from menstrual and peripheral blood and from endometrial biopsy-derived tissue from healthy women to determine the types of T cells present in this compartment. Our data demonstrated that T cells isolated from menstrual blood are a heterogeneous population of cells with markers reminiscent of blood and mucosal cells as well as unique phenotypes not represented in either compartment. T cells isolated from menstrual blood expressed increased levels of HLA-DR, αEβ7 and CXCR4 and reduced levels of CD62L relative to peripheral blood. Menstrual blood CD4+ T cells were enriched for cells expressing both CCR7 and CD45RA, markers identifying naïve T cells and were functional as determined by antigen-specific intracellular cytokine production assays. These data may open new avenues of investigation for cell mediated immune studies involving the female reproductive tract without the need for biopsies

HLA Class-II Associated HIV Polymorphisms Predict Escape from CD4+ T Cell Responses.

Antiretroviral therapy, antibody and CD8+ T cell-mediated responses targeting human immunodeficiency virus-1 (HIV-1) exert selection pressure on the virus necessitating escape; however, the ability of CD4+ T cells to exert selective pressure remains unclear. Using a computational approach on HIV gag/pol/nef sequences and HLA-II allelic data, we identified 29 HLA-II associated HIV sequence polymorphisms or adaptations (HLA-AP) in an African cohort of chronically HIV-infected individuals. Epitopes encompassing the predicted adaptation (AE) or its non-adapted (NAE) version were evaluated for immunogenicity. Using a CD8-depleted IFN-γ ELISpot assay, we determined that the magnitude of CD4+ T cell responses to the predicted epitopes in controllers was higher compared to non-controllers (p<0.0001). However, regardless of the group, the magnitude of responses to AE was lower as compared to NAE (p<0.0001). CD4+ T cell responses in patients with acute HIV infection (AHI) demonstrated poor immunogenicity towards AE as compared to NAE encoded by their transmitted founder virus. Longitudinal data in AHI off antiretroviral therapy demonstrated sequence changes that were biologically confirmed to represent CD4+ escape mutations. These data demonstrate an innovative application of HLA-associated polymorphisms to identify biologically relevant CD4+ epitopes and suggests CD4+ T cells are active participants in driving HIV evolution

A Seasonal Study of Dissolved Cobalt in the Ross Sea, Antarctica: Micronutrient Behavior, Absence of Scavenging, and Relationships with Zd, Cd, and P.

We report the distribution of cobalt (Co) in the Ross Sea polynya during austral summer 2005-2006 and the following austral spring 2006. The vertical distribution of total dissolved Co (dCo) was similar to soluble reactive phosphate (PO(4)(3-)), with dCo and PO(4)(3-) showing a significant correlation throughout the water column (r(2) = 0.87, 164 samples). A strong seasonal signal for dCo was observed, with most spring samples having concentrations ranging from similar to ~ 45-85 pM, whereas summer dCo values were depleted below these levels by biological activity. Surface transect data from the summer cruise revealed concentrations at the low range of this seasonal variability (similar to ~ 30pM dCo), with concentrations as low as 20pM observed in some regions where PO(4)(3-) was depleted to similar to 0.1 mu M. Both complexed Co, defined as the fraction of dCo bound by strong organic ligands, and labile Co, defined as the fraction of dCo not bound by these ligands, were typically observed in significant concentrations throughout the water column. This contrasts the depletion of labile Co observed in the euphotic zone of other ocean regions, suggesting a much higher bioavailability for Co in the Ross Sea. An ecological stoichiometry of 37.6 mu mol Co: mol(-1) PO(4)(3-) calculated from dissolved concentrations was similar to values observed in the subarctic Pacific, but approximately tenfold lower than values in the Eastern Tropical Pacific and Equatorial Atlantic. The ecological stoichiometries for dissolved Co and Zn suggest a greater overall use of Zn relative to Co in the shallow waters of the Ross Sea, with a Co: PO(4)(3-) / Zn: PO(4)(3-) ratio of 1:17. Comparison of these observed stoichiometries with values estimated in culture studies suggests that Zn is a key micronutrient that likely influences phytoplankton diversity in the Ross Sea. In contrast, the observed ecological stoichiometries for Co were below values necessary for the growth of eukaryotic phytoplankton in laboratory culture experiments conducted in the absence of added zinc, implying the need for significant Zn nutrition in the Zn-Co cambialistic enzymes. The lack of an obvious kink in the dissolved Co: PO(4)(3-) relationship was in contrast to Zn: PO(4)(3-) and Cd: wPO(4)(3-) kinks previously observed in the Ross Sea. An excess uptake mechanism for kink formation is proposed as a major driver of Cd: PO(4)(3-) kinks, where Zn and Cd uptake in excess of that needed for optimal growth occurs at the base of the euphotic zone, and no clear Co kink occurs because its abundances are too low for excess uptake. An unusual characteristic of Co geochemistry in the Ross Sea is an apparent lack of Co scavenging processes, as inferred from the absence of dCo removal below the euphotic zone. We hypothesize that this vertical distribution reflects a low rate of Co scavenging by Mn oxidizing bacteria, perhaps due to Mn scarcity, relative to the timescale of the annual deep winter mixing in the Ross Sea. Thus Co exhibits nutrient-like behavior in the Ross Sea, in contrast to its hybrid-type behavior in other ocean regions, with implications for the possibility of increased marine Co inventories and utility as a paleooceanographic proxy

Hydrothermal trace metal release and microbial metabolism in the northeastern Lau Basin of the South Pacific Ocean

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Cohen, N. R., Noble, A. E., Moran, D. M., McIlvin, M. R., Goepfert, T. J., Hawco, N. J., German, C. R., Horner, T. J., Lamborg, C. H., McCrow, J. P., Allen, A. E., & Saito, M. A. Hydrothermal trace metal release and microbial metabolism in the northeastern Lau Basin of the South Pacific Ocean. Biogeosciences, 18(19), (2021): 5397–5422, https://doi.org/10.5194/bg-18-5397-2021.Bioactive trace metals are critical micronutrients for marine microorganisms due to their role in mediating biological redox reactions, and complex biogeochemical processes control their distributions. Hydrothermal vents may represent an important source of metals to microorganisms, especially those inhabiting low-iron waters, such as in the southwest Pacific Ocean. Previous measurements of primordial 3He indicate a significant hydrothermal source originating in the northeastern (NE) Lau Basin, with the plume advecting into the southwest Pacific Ocean at 1500–2000 m depth (Lupton et al., 2004). Studies investigating the long-range transport of trace metals associated with such dispersing plumes are rare, and the biogeochemical impacts on local microbial physiology have not yet been described. Here we quantified dissolved metals and assessed microbial metaproteomes across a transect spanning the tropical and equatorial Pacific with a focus on the hydrothermally active NE Lau Basin and report elevated iron and manganese concentrations across 441 km of the southwest Pacific. The most intense signal was detected near the Mangatolo Triple Junction (MTJ) and Northeast Lau Spreading Center (NELSC), in close proximity to the previously reported 3He signature. Protein content in distal-plume-influenced seawater, which was high in metals, was overall similar to background locations, though key prokaryotic proteins involved in metal and organic uptake, protein degradation, and chemoautotrophy were abundant compared to deep waters outside of the distal plume. Our results demonstrate that trace metals derived from the NE Lau Basin are transported over appreciable distances into the southwest Pacific Ocean and that bioactive chemical resources released from submarine vent systems are utilized by surrounding deep-sea microbes, influencing both their physiology and their contributions to ocean biogeochemical cycling.This research has been supported by the National Science Foundation (grant nos. 1031271, 1924554, 1850719, 1736599, and 1851007); the Gordon and Betty Moore Foundation (grant no. 3782); and the Simons Foundation (grant no. 544236)

A seasonal study of dissolved cobalt in the Ross Sea, Antarctica : micronutrient behavior, absence of scavenging, and relationships with Zn, Cd, and P

© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution 3.0 License. The definitive version was published in Biogeosciences 7 (2010): 4059-4082, doi:10.5194/bg-7-4059-2010.We report the distribution of cobalt (Co) in the Ross Sea polynya during austral summer 2005–2006 and the following austral spring 2006. The vertical distribution of total dissolved Co (dCo) was similar to soluble reactive phosphate (PO43−), with dCo and PO43− showing a significant correlation throughout the water column (r2 = 0.87, 164 samples). A strong seasonal signal for dCo was observed, with most spring samples having concentrations ranging from ~45–85 pM, whereas summer dCo values were depleted below these levels by biological activity. Surface transect data from the summer cruise revealed concentrations at the low range of this seasonal variability (~30 pM dCo), with concentrations as low as 20 pM observed in some regions where PO43− was depleted to ~0.1 μM. Both complexed Co, defined as the fraction of dCo bound by strong organic ligands, and labile Co, defined as the fraction of dCo not bound by these ligands, were typically observed in significant concentrations throughout the water column. This contrasts the depletion of labile Co observed in the euphotic zone of other ocean regions, suggesting a much higher bioavailability for Co in the Ross Sea. An ecological stoichiometry of 37.6 μmol Co:mol−1 PO43− calculated from dissolved concentrations was similar to values observed in the subarctic Pacific, but approximately tenfold lower than values in the Eastern Tropical Pacific and Equatorial Atlantic. The ecological stoichiometries for dissolved Co and Zn suggest a greater overall use of Zn relative to Co in the shallow waters of the Ross Sea, with a Co:PO43−/Zn:PO43− ratio of 1:17. Comparison of these observed stoichiometries with values estimated in culture studies suggests that Zn is a key micronutrient that likely influences phytoplankton diversity in the Ross Sea. In contrast, the observed ecological stoichiometries for Co were below values necessary for the growth of eukaryotic phytoplankton in laboratory culture experiments conducted in the absence of added zinc, implying the need for significant Zn nutrition in the Zn-Co cambialistic enzymes. The lack of an obvious kink in the dissolved Co:PO43− relationship was in contrast to Zn:PO43− and Cd:PO43− kinks previously observed in the Ross Sea. An excess uptake mechanism for kink formation is proposed as a major driver of Cd:PO43− kinks, where Zn and Cd uptake in excess of that needed for optimal growth occurs at the base of the euphotic zone, and no clear Co kink occurs because its abundances are too low for excess uptake. An unusual characteristic of Co geochemistry in the Ross Sea is an apparent lack of Co scavenging processes, as inferred from the absence of dCo removal below the euphotic zone. We hypothesize that this vertical distribution reflects a low rate of Co scavenging by Mn oxidizing bacteria, perhaps due to Mn scarcity, relative to the timescale of the annual deep winter mixing in the Ross Sea. Thus Co exhibits nutrient-like behavior in the Ross Sea, in contrast to its hybrid-type behavior in other ocean regions, with implications for the possibility of increased marine Co inventories and utility as a paleooceanographic proxy.This research was supported by the US National Science Foundation through research grants (OPP-0440840, OPP-0338097, OPP-0732665, OCE-0452883, OCE-0752991, OCE-0928414)

Thaumarchaeal ecotype distributions across the equatorial Pacific Ocean and their potential roles in nitrification and sinking flux attenuation

© The Author(s), 2017. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Limnology and Oceanography 62 (2017): 1984–2003, doi:10.1002/lno.10547.Thaumarchaea are among the most abundant microbial groups in the ocean, but controls on their abundance and the distribution and metabolic potential of different subpopulations are poorly constrained. Here, two ecotypes of ammonia-oxidizing thaumarchaea were quantified using ammonia monooxygenase (amoA) genes across the equatorial Pacific Ocean. The shallow, or water column “A” (WCA), ecotype was the most abundant ecotype at the depths of maximum nitrification rates, and its abundance correlated with other biogeochemical indicators of remineralization such as NO3 : Si and total Hg. Metagenomes contained thaumarchaeal genes encoding for the catalytic subunit of the urease enzyme (ureC) at all depths, suggesting that members of both WCA and the deep, water column “B” (WCB) ecotypes may contain ureC. Coupled urea hydrolysis-ammonia oxidation rates were similar to ammonia oxidation rates alone, suggesting that urea could be an important source of ammonia for mesopelagic ammonia oxidizers. Potential inducement of metal limitation of both ammonia oxidation and urea hydrolysis was demonstrated via additions of a strong metal chelator. The water column inventory of WCA was correlated with the depth-integrated abundance of WCB, with both likely controlled by the flux of sinking particulate organic matter, providing strong evidence of vertical connectivity between the ecotypes. Further, depth-integrated amoA gene abundance and nitrification rates were correlated with particulate organic nitrogen flux measured by contemporaneously deployed sediment traps. Together, the results refine our understanding of the controls on thaumarchaeal distributions in the ocean, and provide new insights on the relationship between material flux and microbial communities in the mesopelagic.United States National Science Foundation (NSF) Grant Numbers: OCE-1260006, OCE-1031271, OCE-1337780, OCE-1259994; University of Maryland Center for Environmental Science (UMCES); JGI Community Sequencing Project 133