“Dr. Sruthi Sundaram has discovered that a common organic solvent prevents preterm birth in an animal model. She has shown that the compound acts by down-regulating pro-inflammatory signaling molecules and simultaneoulsy up-regulating anti-inflammatory mediators. The potential clinical impact of her work is enormous. An editorial accompanying her published paper stated, "...the promise of such an apparently safe and cheap compound that dampens or obviates maternal inflammatory pathology and inhibits preterm delivery is exciting enough. No other factor has shown such promise in terms of treating the inflammatory causes of preterm delivery."”
Sruthi Sundaram, PhD, RAC
Burlington, Massachusetts, United States
854 followers
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About
Experienced Regulatory Affairs Professional with 8 years demonstrated history of…
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I am so thrilled to be a part of this exciting work Mercy is doing in early cancer detection. What an amazing milestone to get the technical concept…
I am so thrilled to be a part of this exciting work Mercy is doing in early cancer detection. What an amazing milestone to get the technical concept…
Liked by Sruthi Sundaram, PhD, RAC
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💡 A Festival of Opportunity at SCDM in Boston 📊 We're forging new connections and learning how AI is driving innovative data management solutions…
💡 A Festival of Opportunity at SCDM in Boston 📊 We're forging new connections and learning how AI is driving innovative data management solutions…
Liked by Sruthi Sundaram, PhD, RAC
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If you're in IVD or LDT leadership roles in QA/RA/CA or are a CEO - join me at AMDM's Focus Meeting on October 17 & 18th, 2024. Learn strategies to…
If you're in IVD or LDT leadership roles in QA/RA/CA or are a CEO - join me at AMDM's Focus Meeting on October 17 & 18th, 2024. Learn strategies to…
Liked by Sruthi Sundaram, PhD, RAC
Experience
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Served as a Judge for animal sciences category
New York State Science and Engineering Fair (NYSSEF)
Education
Publications
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Inhibition of sphingosine kinase prevents lipopolysaccharide-induced preterm birth and suppresses proinflammatory responses in a murine model
American Journal of Pathology
Premature delivery occurs in 12% of all births, and accounts for nearly half of long-term neurological morbidity, and 60% to 80% of perinatal mortality. Despite advances in obstetrics and neonatology, the rate of premature delivery has increased approximately 12% since 1990. The single most common cause of spontaneous preterm birth is infection. Several lines of evidence have demonstrated the role of endothelin-1 as both a constrictor of uterine myometrial smooth muscle and a proinflammatory…
Premature delivery occurs in 12% of all births, and accounts for nearly half of long-term neurological morbidity, and 60% to 80% of perinatal mortality. Despite advances in obstetrics and neonatology, the rate of premature delivery has increased approximately 12% since 1990. The single most common cause of spontaneous preterm birth is infection. Several lines of evidence have demonstrated the role of endothelin-1 as both a constrictor of uterine myometrial smooth muscle and a proinflammatory mediator. Endothelin-1 activates the phospholipase C pathway, leading to activation of protein kinase C and, in turn, sphingosine kinase (SphK). The inhibition of SphK has been recently shown to control the proinflammatory response associated with sepsis. We show herein, for the first time, that SphK inhibition prevents inflammation-associated preterm birth in a murine model. Rescue of pups from premature abortion with an SphK inhibitor occurs by suppression of the proinflammatory cytokines tumor necrosis factor α, Il-1β, and Il-6 and attenuation of polymorphonuclear inflammatory cells into the placental labyrinth. Moreover, we postulate that inhibition of SphK leads to suppression of endothelin-converting enzyme-1 expression, indicating the presence of an endothelin-converting enzyme 1/endothelin 1-SphK positive feedback loop. This work introduces a novel approach for the control of infection-triggered preterm labor, a condition for which there is no effective treatment
Other authorsSee publication -
N,N-Dimethylacetamide Regulates the Proinflammatory Response Associated with Endotoxin and Prevents Preterm Birth
The American Journal of Pathology
The proinflammatory response leads to various types of pathologic pathways, including the development of preterm birth. Preterm birth occurs in 12% of deliveries in the United States and causes more than 70% of perinatal morbidity and mortality. The most common cause of spontaneous preterm birth is intrauterine infection in the mother. There is accumulating evidence indicating that the release of proinflammatory cytokines plays a critical role in the pathogenesis of inflammation-associated…
The proinflammatory response leads to various types of pathologic pathways, including the development of preterm birth. Preterm birth occurs in 12% of deliveries in the United States and causes more than 70% of perinatal morbidity and mortality. The most common cause of spontaneous preterm birth is intrauterine infection in the mother. There is accumulating evidence indicating that the release of proinflammatory cytokines plays a critical role in the pathogenesis of inflammation-associated premature delivery. We found that the common organic solvent, N,N-dimethylacetamide (DMA), prevents endotoxin-induced preterm birth in timed pregnant C57BL/6 embryonic day (E)15.5 mice and rescues their pups from spontaneous abortion at doses many-fold lower than those currently used clinically and in a dose-dependent fashion. We also provide histologic evidence that DMA suppresses the endotoxin-triggered proinflammatory response by significantly attenuating inflammatory cell infiltration of placental tissue. Furthermore, immunoblotting analysis of placental tissue harvested from our murine models revealed DMA-mediated regulation of expression of the proinflammatory cytokines IL-1β, tumor necrosis factor α, and IL-6, and increased expression of the regulatory inflammatory cytokine IL-10. By using in vitro studies, we provide evidence that DMA suppresses macrophage function and that this small molecule prevents nuclear translocation of nuclear factor-kB. These results suggest that DMA represents a newly discovered, nontoxic therapy for a broad range of inflammatory disorders.
Other authorsSee publication -
"N, N−Dimethylacetamide (DMA) Prevents Preterm Birth in a Murine Model by Up−Regulating Interleukin 10
Society for Gynecologic Investigation, 59th Annual Scientific Meeting
The lack of efficacy of anti-inflammatory drugs, antioxidants and other tocolytics in the treatment of preterm delivery (PTD) has shifted interest towards a better understanding of the pathogenesis of PTD, specifically targeting the different pathways believed to be involved.
In this study, the effects of a widely used industrial solvent, N,N-dimethylacetamide (DMA) on PTD was studied. Using a lipopolysaccharide (LPS)-induced (50 mg/kg i.p.) mouse model of PTD, we demonstrated that DMA…The lack of efficacy of anti-inflammatory drugs, antioxidants and other tocolytics in the treatment of preterm delivery (PTD) has shifted interest towards a better understanding of the pathogenesis of PTD, specifically targeting the different pathways believed to be involved.
In this study, the effects of a widely used industrial solvent, N,N-dimethylacetamide (DMA) on PTD was studied. Using a lipopolysaccharide (LPS)-induced (50 mg/kg i.p.) mouse model of PTD, we demonstrated that DMA significantly reduced the incidence of PTD in a dose dependent manner. Pre-treating animals with 1.56 mg/kg DMA before the LPS challenge significantly decreased levels of nuclear factor-κB (NF- κB), interleukin (IL)-6 and tumor necrosis factor-α in the placental tissues compared to controls. Additionally, we also detected increased levels of the anti-inflammatory cytokine IL-10. Histological analysis of placental and uterine sections revealed a decrease in the levels of circulating polymorphonuclear neutrophils. The results suggest that DMA is an effective tocolytic and the proposed mechanism of action is due to its anti-inflammatory effects. In conclusion, DMA was effective in preventing infection-associated PTD and showed a dose response relationship. Further studies are required to determine DMA’s exact mechanism of action and its efficacy to toxicity ratio.Other authors -
Prolactin Controls Infection-Associated Preterm Birth in a Murine Model
Society for Gynecologic Investigation, 58th Annual Scientific Meeting
Preterm birth (PTB) affects nearly 40% of all women. In the United States, 12-13% of births are prematureand PTB accounts for the majority of perinatal morbidity andmortality. Our overlying hypothesis is that prolactin (PRL)can control infection-associated preterm birth. Mice are injected intraperitoneally (ip) with an intermediate dose of lipopolysaccharide (LPS), causing approximately half of the mice to develop preterm birth(PTB) and the other half to carry their pups to term.Oligonucleotide…
Preterm birth (PTB) affects nearly 40% of all women. In the United States, 12-13% of births are prematureand PTB accounts for the majority of perinatal morbidity andmortality. Our overlying hypothesis is that prolactin (PRL)can control infection-associated preterm birth. Mice are injected intraperitoneally (ip) with an intermediate dose of lipopolysaccharide (LPS), causing approximately half of the mice to develop preterm birth(PTB) and the other half to carry their pups to term.Oligonucleotide microarray analysis is performed on gestational tissues collected from the two groups of mice in order to identify “protective” genes that prevent the mice fromdeveloping PTB. In a second line of investigation, in vivo analysis of the effect of PRL on infection-associated PTB is performed. Briefly, E15 C57BL/6 mice are injected with LPS, followed by ip injection of either PRL or vehicle. Mice are then monitored for PTB. Finally, to identify the mechanism by which PRL acts to prevent PTB, Western blot analysis of Jak2 expression is carried out in gestational tissues collected from mice successfully protected from PTB with PRL vs. control mice delivering prematurely.
Microarray analysis of placental tissues shows
statistically significant up-regulation of several PRL family genes (p<0.05) in the mice protected from PTB. Moreover, microarray results show down-regulation of PRL family genes in uterine tissue in mice progressing to PTB (p<0.05). Real
time rt pcr confirms microarray findings. Finally, Western blot analysis shows up-regulation of Jak2 proteins in placental tissue samples of mice protected from PTB by receiving PRL
(p<0.05). Taken together, the data indicate that PRL has a protective effect in controlling the development of infection-associated PTB. This action likely occurs via PRL- R receptors present in the decidua, where STAT5 proteins may be activated upon receptor activation by PRL, which
leads to the prototype Jak2/STAT5 signaling cascade.Other authors
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Anatomy Physiology
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Applied Biochemistry
PHS-212
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Intro to Biotechnology
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Laboratory use of Radiotracers
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Regulatory and Ethical Challenge
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DMA controls infection associated preterm birth in a murine model
- Present
The two statements that are inevitable when we talk about preterm birth (PTB) are that : 1. PTB is the leading cause of neonatal morbidity and mortality, 2. It is difficult to identify the cause of PTB and therefore find a suitable tocolytic to prevent it. This inspired me to take PTB as my topic for research, and in the course of time I accidentally discovered that a small molecule solvent 'DMA' was successful in preventing PTB in a murine model possibly via an anti-inflammatory pathway.
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