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3. Compartmentalized ocular lymphatic system mediates eye–brain immunity

Author

Yin, Xiangyun, Zhang, Sophia, Lee, Ju Hyun, Dong, Huiping, Mourgkos, George, Terwilliger, Gordon, Kraus, Aurora, Geraldo, Luiz Henrique, Poulet, Mathilde, Fischer, Suzanne, Zhou, Ting, Mohammed, Farrah Shalima, Zhou, Jiangbing, Wang, Yongfu, Malloy, Seth, Rohner, Nicolas, Sharma, Lokesh, Salinas, Irene, Eichmann, Anne, Thomas, Jean-Leon, Saltzman, W. Mark, Huttner, Anita, Zeiss, Caroline, Ring, Aaron, Iwasaki, Akiko, and Song, Eric

Published
2024
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6. The NIH Somatic Cell Genome Editing program

Author

Saha, Krishanu, Sontheimer, Erik J, Brooks, PJ, Dwinell, Melinda R, Gersbach, Charles A, Liu, David R, Murray, Stephen A, Tsai, Shengdar Q, Wilson, Ross C, Anderson, Daniel G, Asokan, Aravind, Banfield, Jillian F, Bankiewicz, Krystof S, Bao, Gang, Bulte, Jeff WM, Bursac, Nenad, Campbell, Jarryd M, Carlson, Daniel F, Chaikof, Elliot L, Chen, Zheng-Yi, Cheng, R Holland, Clark, Karl J, Curiel, David T, Dahlman, James E, Deverman, Benjamin E, Dickinson, Mary E, Doudna, Jennifer A, Ekker, Stephen C, Emborg, Marina E, Feng, Guoping, Freedman, Benjamin S, Gamm, David M, Gao, Guangping, Ghiran, Ionita C, Glazer, Peter M, Gong, Shaoqin, Heaney, Jason D, Hennebold, Jon D, Hinson, John T, Khvorova, Anastasia, Kiani, Samira, Lagor, William R, Lam, Kit S, Leong, Kam W, Levine, Jon E, Lewis, Jennifer A, Lutz, Cathleen M, Ly, Danith H, Maragh, Samantha, McCray, Paul B, McDevitt, Todd C, Mirochnitchenko, Oleg, Morizane, Ryuji, Murthy, Niren, Prather, Randall S, Ronald, John A, Roy, Subhojit, Roy, Sushmita, Sabbisetti, Venkata, Saltzman, W Mark, Santangelo, Philip J, Segal, David J, Shimoyama, Mary, Skala, Melissa C, Tarantal, Alice F, Tilton, John C, Truskey, George A, Vandsburger, Moriel, Watts, Jonathan K, Wells, Kevin D, Wolfe, Scot A, Xu, Qiaobing, Xue, Wen, Yi, Guohua, and Zhou, Jiangbing

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biotechnology, Human Genome, Gene Therapy, 5.2 Cellular and gene therapies, Generic health relevance, Animals, Cells, Gene Editing, Genetic Therapy, Genome, Human, Goals, Humans, National Institutes of Health (U.S.), United States, SCGE Consortium, General Science & Technology
Abstract

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.

Published
2021

20. Pilot PET study of vaginally administered bioadhesive nanoparticles in cynomolgus monkeys: Kinetics and safety evaluation

Author

Grun, Molly K., primary, Honhar, Praveen, additional, Wang, Yazhe, additional, Rossano, Samantha, additional, Khang, Minsoo, additional, Suh, Hee Won, additional, Fowles, Krista, additional, Kliman, Harvey J., additional, Cavaliere, Alessandra, additional, Carson, Richard E., additional, Marquez‐Nostra, Bernadette, additional, and Saltzman, W. Mark, additional

Published
2024
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25. Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance

Author

Wang, Yongheng, Jiang, Yuhang, Wei, Dengshuai, Singh, Priya, Yu, Yingjie, Lee, Teresa, Zhang, Lingpu, Mandl, Hanna K., Piotrowski-Daspit, Alexandra S., Chen, Xinyuan, Li, Fan, Li, Xing, Cheng, Yiyu, Josowitz, Alexander, Yang, Fan, Zhao, Yao, Wang, Fuyi, Zhao, Zhenwen, Huttner, Anita, Bindra, Ranjit S., Xiao, Haihua, and Mark Saltzman, W.

Published
2021
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26. Nanoparticles for delivery of agents to fetal lungs

Author

Ullrich, Sarah J., Freedman-Weiss, Mollie, Ahle, Samantha, Mandl, Hanna K., Piotrowski-Daspit, Alexandra S., Roberts, Katherine, Yung, Nicholas, Maassel, Nathan, Bauer-Pisani, Tory, Ricciardi, Adele S., Egan, Marie E., Glazer, Peter M., Saltzman, W. Mark, and Stitelman, David H.

Published
2021
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27. Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys

Author

DiRito, Jenna R., Hosgood, Sarah A., Reschke, Melanie, Albert, Claire, Bracaglia, Laura G., Ferdinand, John R., Stewart, Benjamin J., Edwards, Christopher M., Vaish, Anand G., Thiru, Sathia, Mulligan, David C., Haakinson, Danielle J., Clatworthy, Menna R., Saltzman, W. Mark, Pober, Jordan S., Nicholson, Michael L., and Tietjen, Gregory T.

Published
2021
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29. Effects of Reproductive Experience on Central Expression of Progesterone, Oestrogen α, Oxytocin and Vasopressin Receptor mRNA in Male California Mice (Peromyscus californicus)

Author

Perea‐Rodriguez, JP, Takahashi, EY, Amador, TM, Hao, RC, Saltzman, W, and Trainor, BC

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Behavioral and Social Science, Estrogen, Neurological, Animals, Behavior, Animal, Estrogen Receptor alpha, Female, Male, Paternal Behavior, Peromyscus, RNA, Messenger, Receptors, Oxytocin, Receptors, Progesterone, Receptors, Vasopressin, Reproduction, Sex Characteristics, oestrogens, oxytocin, progestogens, vasopressin, paternal care, fatherhood, Endocrinology & Metabolism, Clinical sciences
Abstract

Fatherhood in biparental mammals is accompanied by distinct neuroendocrine changes in males, involving some of the same hormones involved in maternal care. In the monogamous, biparental California mouse (Peromyscus californicus), paternal care has been linked to changes in the central and/or peripheral availability of oestrogen, progesterone, vasopressin and oxytocin, although it is not known whether these endocrine fluctuations are associated with changes in receptor availability in the brain. Thus, we compared mRNA expression of oestrogen receptor (ER)α, progesterone receptor (PR), vasopressin receptor (V1a) and oxytocin receptor (OTR) in brain regions implicated in paternal care [i.e. medial preoptic area (MPOA)], fear [i.e. medial amygdala (MeA)] and anxiety [i.e. bed nucleus of the stria terminalis (BNST)] between first-time fathers (n = 8) and age-matched virgin males (n = 7). Males from both reproductive conditions behaved paternally towards unrelated pups, whereas fathers showed significantly shorter latencies to behave paternally and less time investigating pups. Furthermore, fathers showed significantly lower PR, OTR and V1a receptor mRNA expression in the BNST compared to virgins. Fathers also showed a marginally significant (P = 0.07) reduction in progesterone receptor mRNA expression in the MPOA, although fatherhood was not associated with any other changes in receptor mRNA in the MPOA or MeA. The results of the present study indicate that behavioural and endocrine changes associated with the onset of fatherhood, and/or with cohabitation with a (breeding) female, are accompanied by changes in mRNA expression of hormone and neuropeptide receptors in the brain.

Published
2015

36. Functional Significance of Hormonal Changes in Mammalian Fathers

Author

Saltzman, W and Ziegler, TE

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Behavioral and Social Science, Generic health relevance, Animals, Behavior, Animal, Fathers, Hormones, Male, Neuronal Plasticity, biparental care, paternal behaviour, energy balance, stress, anxiety, neurogenesis, Endocrinology & Metabolism, Clinical sciences
Abstract

In the 5-10% of mammals in which both parents routinely provide infant care, fathers as well as mothers undergo systematic endocrine changes as they transition into parenthood. Although fatherhood-associated changes in such hormones and neuropeptides as prolactin, testosterone, glucocorticoids, vasopressin and oxytocin have been characterised in only a small number of biparental rodents and primates, they appear to be more variable than corresponding changes in mothers, and experimental studies typically have not provided strong or consistent evidence that these endocrine shifts play causal roles in the activation of paternal care. Consequently, their functional significance remains unclear. We propose that endocrine changes in mammalian fathers may enable males to meet the species-specific demands of fatherhood by influencing diverse aspects of their behaviour and physiology, similar to many effects of hormones and neuropeptides in mothers. We review the evidence for such effects, focusing on recent studies investigating whether mammalian fathers in biparental species undergo systematic changes in (i) energetics and body composition; (ii) neural plasticity, cognition and sensory physiology; and (iii) stress responsiveness and emotionality, all of which may be mediated by endocrine changes. The few published studies, based on a small number of rodent and primate species, suggest that hormonal and neuropeptide alterations in mammalian fathers might mediate shifts in paternal energy balance, body composition and neural plasticity, although they do not appear to have major effects on stress responsiveness or emotionality. Further research is needed on a wider variety of biparental mammals, under more naturalistic conditions, to more fully determine the functional significance of hormone and neuropeptide profiles of mammalian fatherhood and to clarify how fatherhood may trade off with (or perhaps enhance) aspects of organismal function in biparental mammals.

Published
2014

37. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A

Author

Gupta, Romi, Dong, Yuying, Solomon, Peter D, Wettersten, Hiromi I, Cheng, Christopher J, Min, Jin-Na, Henson, Jeremy, Dogra, Shaillay Kumar, Hwang, Sung H, Hammock, Bruce D, Zhu, Lihua J, Reddel, Roger R, Saltzman, W Mark, Weiss, Robert H, Chang, Sandy, Green, Michael R, and Wajapeyee, Narendra

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biological Sciences, Cancer, Genetics, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Animals, Apoptosis, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, Humans, Mice, Mice, Nude, Mutation, Neoplasms, Experimental, Telomerase, Tumor Suppressor Protein p53
Abstract

Tumor suppressor p53 plays an important role in mediating growth inhibition upon telomere dysfunction. Here, we show that loss of the p53 target gene cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21(WAF1/CIP1)) increases apoptosis induction following telomerase inhibition in a variety of cancer cell lines and mouse xenografts. This effect is highly specific to p21, as loss of other checkpoint proteins and CDK inhibitors did not affect apoptosis. In telomerase, inhibited cell loss of p21 leads to E2F1- and p53-mediated transcriptional activation of p53-upregulated modulator of apoptosis, resulting in increased apoptosis. Combined genetic or pharmacological inhibition of telomerase and p21 synergistically suppresses tumor growth. Furthermore, we demonstrate that simultaneous inhibition of telomerase and p21 also suppresses growth of tumors containing mutant p53 following pharmacological restoration of p53 activity. Collectively, our results establish that inactivation of p21 leads to increased apoptosis upon telomerase inhibition and thus identify a genetic vulnerability that can be exploited to treat many human cancers containing either wild-type or mutant p53.

Published
2014

39. Intrathecal delivery of nanoparticle PARP inhibitor to the cerebrospinal fluid for the treatment of metastatic medulloblastoma

Author

Khang, Minsoo, primary, Lee, Ju Hyun, additional, Lee, Teresa, additional, Suh, Hee-Won, additional, Lee, Supum, additional, Cavaliere, Alessandra, additional, Rushing, Amy, additional, Geraldo, Luiz H., additional, Belitzky, Erika, additional, Rossano, Samantha, additional, de Feyter, Henk M., additional, Shin, Kwangsoo, additional, Huttner, Anita, additional, Roussel, Martine F., additional, Thomas, Jean-Leon, additional, Carson, Richard E., additional, Marquez-Nostra, Bernadette, additional, Bindra, Ranjit S., additional, and Saltzman, W. Mark, additional

Published
2023
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46. Physiological and neuroendocrine responses to chronic variable stress in male California mice (Peromyscus californicus): Influence of social environment and paternal state

Author

De Jong, TR, Harris, BN, Perea-Rodriguez, JP, and Saltzman, W

Subjects
Biomedical and Clinical Sciences, Pediatric, Behavioral and Social Science, Mental Health, Basic Behavioral and Social Science, Animals, Chronic Disease, Corticosterone, Female, Male, Neurosecretory Systems, Pair Bond, Paternal Behavior, Peromyscus, Reproduction, Social Environment, Stress, Psychological, Time Factors, Chronic variable stress, Biparental, Monogamous, Peromyscus californicus, CRH, AVP, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry, Biomedical and clinical sciences, Psychology
Abstract

Social environment and parental state affect stress responses in mammals, but their impact may depend on the social and reproductive strategy of the species. The influences of cohabitation with a male or female conspecific, and the birth of offspring, on the physiological and endocrine responses to chronic variable stress were studied in the monogamous and biparental California mouse (Peromyscus californicus). Adult male California mice were housed either with a male cage mate (virgin males, VM), a female cage mate (pair-bonded males, PBM), or a female cage mate and their first newborn litter (new fathers, NF). VM, PBM and NF underwent a 7-day chronic variable stress paradigm (CVS, three stressors per day at semi-random times, n=7-8 per housing condition). Compared to control males (CON, n=6-7 per housing condition), CVS caused loss of body mass, increased basal plasma corticosterone concentrations, and increased basal expression of arginine vasopressin (AVP) mRNA in the paraventricular nucleus of the hypothalamus (PVN). These effects were independent of housing condition. Neither CVS nor housing condition altered novel-stressor-induced corticosterone release, spleen or testis mass, or basal expression of corticotropin-releasing hormone (CRH) mRNA in the PVN. Although CVS appeared to increase adrenal mass and reduce thymus mass specifically in NF, these effects were explained by the lower adrenal mass and higher thymus mass of NF compared to PBM and VM under control conditions. These results suggest that neither engaging in a pair bond nor becoming a father attenuates typical responses to CVS, but that fatherhood may provide a buffer against transient mild stressors (i.e., weighing and blood sampling in the control groups) in this monogamous and biparental rodent.

Published
2013

49. Polymer nanoparticles deliver mRNA to the lung for mucosal vaccination

Author

Suberi, Alexandra, primary, Grun, Molly K., additional, Mao, Tianyang, additional, Israelow, Benjamin, additional, Reschke, Melanie, additional, Grundler, Julian, additional, Akhtar, Laiba, additional, Lee, Teresa, additional, Shin, Kwangsoo, additional, Piotrowski-Daspit, Alexandra S., additional, Homer, Robert J., additional, Iwasaki, Akiko, additional, Suh, Hee-Won, additional, and Saltzman, W. Mark, additional

Published
2023
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