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• Pati, Niladri Bhusan; Jin, Yixin; Kumar, Suman; Kyte, Jon A & Ciosk, Rafal (2025). Thermal potentiation improves IFN-γ production but not cytotoxicity in human CAR-T cells. BMC Research Notes. 18(1). doi: 10.1186/s13104-025-07249-5. Full text in Research Archive Show summary

  Objective Body temperature plays an important role in cancer, with febrile temperature generally associated with improved cancer resistance. In murine models, this resistance has been linked to the cytotoxic T cells, whose differentiation into cancer-killing effector cells is poor at lower but robust at elevated temperatures. If conserved, temperature-mediated potentiation of patient-derived T cells could be implemented to improve the existing cancer treatments, including the chimeric antigen receptor T-cell therapy (CAR T-cell therapy). Here, we tested this possibility using human STEAP1 CAR-T cells developed to target prostate cancer. Results In mice, transient exposure to febrile temperature (39–40 ºC) increases the production of IFN-γ and the cancer-killing ability of CD8 + T cells. Using a similar temperature treatment, we observed elevated levels of IFN-γ also in the human CAR-T cells. However, these cells displayed no improvement in their ability to kill cancer cells. Although we cannot discount the possibility that alternative protocols might lead to other outcomes, our findings suggest that incorporating thermal potentiation into existing protocols of CAR-T cell therapy may be more complicated than anticipated.

• Seybold, Anna Cosima; Kumar, Suman; Tumu, Sharat Chandra & Hausen, Harald (2024). Neurons with larval synaptic targets pioneer the later nervous system in the annelid Malacoceros fuliginosus. Frontiers in Neuroscience. ISSN 1662-4548. 18. doi: 10.3389/fnins.2024.1439897. Full text in Research Archive Show summary

  Comparative studies on the development of nervous systems have a significant impact on understanding animal nervous system evolution. Nevertheless, an important question is to what degree neuronal structures, which play an important role in early stages, become part of the adult nervous system or are relevant for its formation. This is likely in many direct developers, but it is not the case in forms with catastrophic metamorphosis. It is not clear in many forms with gradual metamorphosis. This introduces uncertainty in tracing the evolution of nervous systems and of larval forms. One of the prominent larval characteristics of numerous planktonic marine organisms is the epidermal ciliation used for swimming and steering, which disappears during metamorphosis. Therefore, the neuronal elements controlling the ciliary beating are often assumed to vanish with the cilia and regarded as purely larval specializations. With volume EM, we followed the neuronal targets of the very first pioneer neurons at the apical and posterior ends of the larva of the annelid Malacoceros fuliginosus. We observed that all of these pioneers appear to have a dual function. Although they are laying the paths for the later adult nervous system, they also make synaptic contact with the main ciliated ring of the larva. We propose that the formation of the later adult nervous system and the innervation of the larval locomotory organ are indeed closely linked to each other. This has implications for understanding the early nervous system development of marine larvae and for existing hypotheses on nervous system evolution.

• Kumar, Suman; Tumu, Sharat Chandra; Helm, Conrad & Hausen, Harald (2020). The development of early pioneer neurons in the annelid Malacoceros fuliginosus. BMC Evolutionary Biology. 20(117). doi: 10.1186/s12862-020-01680-x. Full text in Research Archive Show summary

  Background Nervous system development is an interplay of many processes: the formation of individual neurons, which depends on whole-body and local patterning processes, and the coordinated growth of neurites and synapse formation. While knowledge of neural patterning in several animal groups is increasing, data on pioneer neurons that create the early axonal scaffold are scarce. Here we studied the first steps of nervous system development in the annelid Malacoceros fuliginosus. Results We performed a dense expression profiling of a broad set of neural genes. We found that SoxB expression begins at 4 h postfertilization, and shortly later, the neuronal progenitors can be identified at the anterior and the posterior pole by the transient and dynamic expression of proneural genes. At 9 hpf, the first neuronal cells start differentiating, and we provide a detailed description of axonal outgrowth of the pioneer neurons that create the primary neuronal scaffold. Tracing back the clonal origin of the ventral nerve cord pioneer neuron revealed that it is a descendant of the blastomere 2d (2d221), which after 7 cleavages starts expressing Neurogenin, Acheate-Scute and NeuroD. Conclusions We propose that an anterior and posterior origin of the nervous system is ancestral in annelids. We suggest that closer examination of the first pioneer neurons will be valuable in better understanding of nervous system development in spirally cleaving animals, to determine the potential role of cell-intrinsic properties in neuronal specification and to resolve the evolution of nervous systems.

• Hausen, Harald; Döring, Clemens; Kumar, Suman & Tumu, Sharat Chandra (2020). The visual pigment xenopsin is widespread in protostome eyes and impacts the view on eye evolution. eLIFE. 9, p. 1–23. doi: 10.7554/eLife.55193. Full text in Research Archive Show summary

  Photoreceptor cells in the eyes of Bilateria are often classified into microvillar cells with rhabdomeric opsin and ciliary cells with ciliary opsin, each type having specialized molecular components and physiology. First data on the recently discovered xenopsin point towards a more complex situation in protostomes. In this study, we provide clear evidence that xenopsin enters cilia in the eye of the larval bryozoan Tricellaria inopinata and triggers phototaxis. As reported from a mollusc, we find xenopsin coexpressed with rhabdomeric-opsin in eye photoreceptor cells bearing both microvilli and cilia in larva of the annelid Malacoceros fuliginosus. This is the first organism known to have both xenopsin and ciliary opsin, showing that these opsins are not necessarily mutually exclusive. Compiling existing data, we propose that xenopsin may play an important role in many protostome eyes and provides new insights into the function, evolution, and possible plasticity of animal eye photoreceptor cells.

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• Kumar, Suman & Hausen, Harald (2019). Evolutionary and developmental perspective on annelid eye and nervous system: Insights from Malacoceros fuliginosus. Universitetet i Bergen. Full text in Research Archive Show summary

  Eye evolution is far from resolved and despite the considerable interest and decades of study, many questions remain on the evolutionary scenarios of eyes and photoreceptor cells. While examining their ultrastructure has been an important way for comparative studies, the high degree of variation of eye structures/complexities within species (and closely related species) calls for more detailed studies at the molecular level. As with many lophotrochozoan taxa, annelids also display simple to elaborate eye structures. Although general homology of the cerebral rhabdomeric eyes is assumed, this has not been firmly established leaving the scene in the annelid ancestor unanswered. To gain an understanding of the situation in a long pelagic annelid larva, we studied Malacoceros fuliginosus. The larvae possess multiple eyespots and therefore suitable for studies on how different eyespots develop and integrate into the nervous system. We used ultrastructure and gene expression studies to understand the eyespot structure and development. Our phylogenetic analysis of annelid r-opsins revealed the existence of two r-opsin paralogs - r-opsin1 and r-opsin3 within the two main annelid groups - sedentaria and errantia, whereas in basal branching annelids only a single r-opsin type is present. In comparison with the well-studied annelid Platynereis dumerilii, we find that the rhabdomeric eyes have several similarities in terms of spatial and temporal development, r-opsin expression dynamics and axonal connectivity. This suggests homology of the two rhabdomeric eyes and the more complex dorsal eyes in P. dumerilii is likely a case of augmentation of a simple eyespot. Apart from visual r-opsins, the eye PRCs in M. fuliginosus also expresses the newly classified opsin type, xenopsin. Inspection of the eye structure also revealed the existence of a prominent cilium in both rhabdomeric eyes. Additionally, we also identified a c-opsin in an extraocular cell type thereby making it the only species so far having both c-opsin and xenopsin. Taken together, our data provide insights into the eye organization of the annelid ancestor and adds information on how eye evolution is shaped by opsin gain and loss. The second topic of interest is the nervous system development in the M. fuliginosus larva. The evolution of the bilaterian nervous system is a topic of long-standing debate inciting the need for studies at multiple levels along with broader species sampling. A major question is whether the centralized nervous system seen across taxa is derived from a common ancestor or independently originated multiple times. Characterization of the nervous system has been mainly done at the level of gene expression patterns along the major body axes, anterior-posterior and dorsal-ventral. One aspect that has been overlooked particularly in lophotrochozoans is the development of pioneer neurons that give rise to the early neuronal scaffold. In M. fuliginosus, we identify at least three pioneer neurons that are responsible to form the complete early neuronal scaffold. While a posterior neuron pioneers the path for the ventral nerve cord, pair of neurons form the prototroch ring nerve and a ganglion cell near the apical organ with descending axons prefigures the central ganglia. Here we focused on the development of the posterior pioneer neuron and distinguish it from the rest of the neurons. It is one of the earliest cells to differentiate along with other ciliated cells of apical tuft and prototroch cells which are known to have mosaic development. The posterior neuron does not express the well-characterized proneural genes such as Ascl1, Olig, NeuroD, and Ngn and moreover, they even lack Prox1 and Elav which are represented by most other neurons. From a molecular perspective, the posterior pioneer neuron is indeed distinct from the rest of the neurons and may develop in a cell-autonomous manner.

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