Harikrishnan Parameswaran Download

Harikrishnan Parameswaran

Assistant Professor,  Bioengineering

Contact

Office

  • 617.373.7049

Lab

  • Breathe Lab

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Research Focus

We study cell-cell and cell-extracellular matrix interactions in the airway to understand the fundamental mechanisms that regulate airway caliber and why they fail in diseases like asthma.

Education

  • NIH K99 Postdoctoral fellow, Boston University (Mentor: Dr. Kenneth Lutchen)
  • Ph.D., Biomedical Engineering, Boston University (Advisor: Dr. Bela Suki)
  • M.S, Biomedical Engineering, Boston University.
  • B.Tech, Electronics & Telecommunication,  College of Engineering, Trivandrum, Kerala, India

Honors & Awards

  •  Principal Investigator on NIH K99/R00 Award from National Heart, Lung and Blood Institute, (2017)
  • Principal Investigator on NIH R21 Award from National Heart, Lung, and Blood Institute, (2017)
  • Principal investigator on Tier 1 award from Northeastern University, (2019)
  • co-Investigator on NIH R01 from the National Institute of General Medical Sciences, (2020)
  • Principal Investigator on NSF CAREER Award from CMMI (Mechanobiology), (2021)

Teaching Interests

BIOE 5440: Cell as a Machine.

BIOE 5800: Systems, Signals, and Controls for Bioengineers

GE2361: Math Methods in Bioengineering.

Professional Affiliations

American Thoracic Society (Program committee member 2011-2018)

Biomedical Engineering Society Member.

Research Overview

We study cell-cell and cell-extracellular matrix interactions in the airway to understand the fundamental mechanisms that regulate airway caliber and why they fail in diseases like asthma.

Asthma affects over 40 million people in the United States and 300 million worldwide1. In the US alone, the health care cost of asthma exceeds 80 billion dollars annually2. Despite its prevalence and cost burden, treatment for this disease has seen very little change over 50 years. The current therapeutic standard, which targets airway smooth muscle force and airway inflammation, aims to prevent the recurrence of symptoms and does not stop the decline in lung function. In severe asthma, current therapies fail in providing any relief to the patient3. This suggests that there are mechanisms at play that are insensitive to current asthma therapies but predominant, nonetheless.

Research from our lab has revealed that pathological changes occurring in the extracellular matrix ( a meshwork of collagen, enzymes, and proteins that surrounds and supports cells in tissue) can drive healthy human airway smooth muscle cells to become hypercontractile, as seen in asthma.

Breathe Lab

We study cell-cell and cell-extracellular matrix interactions in the airway to understand the fundamental mechanisms that regulate airway caliber and why they fail in diseases like asthma.

Breathe Lab

Selected Research Projects

  • Elucidating the Role of Collective Cell-Matrix Interactions in the Mechanobiology of Airway Narrowing
    • – Principal Investigator, National Science Foundation, CAREER Award
  •  Advanced Image-Based Approach to Assess How Fibrillar Collagen Modulates Airway Reactivity
    • -Principal Investigator, R21 Award, National Institutes of Health
  • Extracellular Determinants of Airway Smooth Muscle Force: A New Paradigm for Sustained Airway Constriction
    • – Principal Investigator, R00 Award, National Institutes of Health

Department Research Areas

Peer Reviewed Journal Articles

2021

  1. Stiffening of the Extracellular Matrix is a Sufficient Condition for Airway Hyperreactivity. R.R Jamieson, S.E Stasiak, S. R. Polio, C McCormick, R.D Auspsburg, J.W Ruberti, and H. Parameswaran Journal of Applied Physiology.  March 2021.

[Chosen for APS select, the American Physiological Society’s collection of best physiology papers]

2020

2. Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells. S.E Stasiak, R.R Jamieson, J. Bouffard, E.J. Cram and Parameswaran Science Advances. Aug 5 2020.

3. Intercellular adhesion stiffness moderates cell decoupling as a function of substrate stiffness D. A. Vargas*, T. Heck, B. Smeets, H. Ramon, Parameswaran and H. Van Oosterwyck Biophysical Journal. July 2020, 119(2):243-257

*  First author was a visiting scholar in my lab during the summer of 2018

2019

4. Extracellular matrix regulates force transmission pathways in multicellular ensembles of human airway smooth muscle cells. S.R Polio, S.E Stasiak, R Krishnan and Parameswaran Sci Rep. 2019 Jul 2;9(1):9564.

  1. CT Imaging-Based Low-Attenuation Super Clusters in Three Dimensions and the Progression of Emphysema. Mondoñedo JR*, Sato S, Oguma T, Muro S, Sonnenberg AH, Zeldich D, Parameswaran, Hirai T, Suki B. Chest. 2019 Jan;155(1):79-87.

*  First author was advised by HP as a Ph.D. thesis committee member.

2018

6 The Digestive Protease Role for Cela1 in Postnatal Lung Matrix Remodeling and AAT-Deficient Emphysema R. Joshi, A. Heinz, Q Fan, S Guo, B Monia, C.E.H. Schmelzer, A.S. Weiss, M.Batie, Parameswaran, B.M.Varisco. Am J Respir Cell Mol Biol. 2018 Aug;59(2):167-178.

  1. Blood pressure-induced physiological strain variability modulates wall structure and function in aorta rings. Imsirovic J, Bartolák-Suki E, Jawde SB, Parameswaran H, Suki B Physiol Meas. 2018 Oct 30;39(10):105014.

 

2016

8 Regulatory Roles of Fluctuation-Driven Mechanotransduction in Cell Function. Suki B, Parameswaran H, Imsirovic J, Bartolák-Suki E. Physiology (Bethesda). 2016 Sep;31(5):346-58

9. Mitochondrial iron chelation ameliorates cigarette smoke–induced bronchitis and emphysema in mice M Cloonan, K.Glass, A.R. Bhashyam, M.E Laucho-Contreras, M. Cervo, M.A Pabon, C. Konrad, F. Polverino, K. Miziumura, M. Ghosh, Parameswaran, N.M Williams, K.T. Rooney, Z.H Chen, M.P. Goldklang, G.Yuan, S.C Moore, D.L. Demeo, T.A. Rouault, J.M. D’Armiento, E.A Schon, G. Manfredi, J. Quackenbush, A. Mahmood, Edwin .K. Silverman, C.A. Owen and Augustine M. Choi.  Nature Medicine 22, 163–174 (2016)

10. Mechanical forces accelerate collagen digestion by bacterial collagenase in lung tissue strips. E.Yi, S. Sato, A Takahashi, Parameswaran, TA Blute, E.B.Suki, B Suki Front. Physiol., (2016)

 

2015

11. Linking ventilation heterogeneity quantified via hyperpolarized 3He MRI to dynamic lung mechanics and airway hyperresponsiveness J.Liu, Parameswaran, M.S. Albert, K.R. Lutchen PLoS ONE 10(11): e0142738.

12. Can Breathing-Like Pressure Oscillations Reverse or Prevent Narrowing of Small Intact Airways? B. Harvey, Parameswaran and K.R. Lutchen J. Appl. Physiol. 2015.

13. Scale Dependence of Structure-Function Relationship in the Emphysematous Mouse Lung S. Sato, E.B. Suki, Parameswaran, H. Hamakawa and B. Suki Front. Physiol. 6:146. 2015.

14. Fluctuation-driven mechanotransduction regulates mitochondrial-network structure and function E.B.Suki, J. Imsirovic, Parameswaran, T. Wellman, N Martinez, P.G. Allen, U. Frey and B. Suki. Nature Materials. 2015 Jul 27

15. Lung structure and function in elastase-treated rats: A follow-up study. M.V. Szabari, J. Tolnai, B.A. Maár, Parameswaran, E. Bartolák-Suki, B. Suki and Z. Hantos. Respir Physiol Neurobiol. 2015.

2014

16. A computational model of the response of adherent cells to stretch and changes in substrate stiffness Parameswaran, K.R. Lutchen and B. Suki J. Appl. Physiol. 116: 825-34, 2014.

17. Topographical control of multiple cell adhesion molecules for traction force microscopy S.R. Polio, Parameswaran, E.P. Canovic, D. Stamenovic, M.L. Smith Integrative Biology 6(3): 357-65, 2014

18. Proteoglycans maintain lung stability in an elastase-treated mouse model of emphysema. A. Takahashi, A. Majumdar, Parameswaran, E.B. Suki and B Suki. Am. J. Respir. Cell Mol. Biol. 51(1): 26-33, 2014

19. Computational modeling helps uncover mechanisms related to the progression of emphysema. B. Suki and Parameswaran Drug Discov. Today 70(27-28): 4245-4249, 2014

20. JNK suppresses pulmonary fibroblast elastogenesis during alveolar development. S. Liu, Parameswaran, S.M. Young and B. Varisco. Resp. Res. 15: 34, 2014

 

2013

21. Semiautomatic segmentation of ventilated airspaces in healthy and asthmatic subjects using hyperpolarized (3)He MRI.  J.K. Lui, A.S. Laprad, H. Parameswaran, Y. Sun, M.S. Albert and K.R. Lutchen. Comput. Math. Methods. Med. Mar 31 2013.

22. Can Tidal Breathing with Deep Inspirations of Intact Airways Create Sustained Bronchoprotection or Bronchodilation? B. Harvey, Parameswaran, K.R. Lutchen J. Appl Physiol. May 30 2013.

23. Emphysema and Mechanical Stress-induced Lung Remodeling B. Suki, S. Sato, Parameswaran, M.V. Szabari, A. Takahashi, and E.B. Suki. Physiology June 2013.

 

2012

24 Acute mechanical forces cause deterioration in lung structure and function in elastase-induced emphysema. M.V. Szabari, Parameswaran, S. Sato, Z. Hantos, E.B. Suki and B. Suki. Am J Physiol Lung Cell Mol Physiol. Oct 2012

25 Functional and morphological assessment of early impairment of airway function in a rat model of emphysema. J. Tolnai, M.V. Szabari, G. Albu, B. Maar, H. Parameswaran, E.B. Suki, B. Suki and Z Hantos. Appl. Physiol. Jun 2012

26 Jamming dynamics of stretch-induced surfactant release by alveolar type II cells. A. Majumdar, S.P. Arold, E. B. Suki, Parameswaran, and B. Suki J. Appl. Physiol, Oct 2011.

 

2011

27 Linking Microscopic Patterns of Tissue Destruction in Emphysema to Macroscopic Stiffness Decline using a Three-Dimensional Computational Model. Parameswaran, A. Majumdar and B. Suki. PLoS Computational Biol. 7(4), April 2011.

28 Dynamics of Enzymatic Digestion of Elastic Fibers and Networks under Tension. A. Araujo, A. Majumdar, Parameswaran, E. Yi, J. Spencer, M. Nugent and B. Suki. Proc. Natl. Acad. Sci. USA. May 2011.

29. Structure-function relations in an elastase-induced mouse model of emphysema H. Hamakawa, E.B. Suki, Parameswaran, A. Majumdar, K. Lutchen, B. Suki. Am. J. Respir. Cell Mol. Biol. Sept. 2011 [HP’s work was featured on the cover]

30. Microtubule dynamics regulate cyclic stretch- induced cell alignment in human airway smooth muscle cells,Morioka*, H. Parameswaran* K. Naruse, M. Kondo, M. Sokabe, Y. Hasegawa, B. Suki, and S. Ito PLoS-ONE 6(10), October 2011.(* Equal Contribution)

31. Mechanical failure, Stress Redistribution, Elastase Activity and Binding Site Availability on Elastin During the Progression of Emphysema. Suki, R. Jesudason, S. Sato, H. Parameswaran, A.D. Araujo, A. Majumdar, P.G. Allen, E. Bartolak-Suki Pulm. Pharmacol. Ther.  April 2011.

 

2010

32. Mechanical forces regulate elastase activity and Binding site availability in lung elastin, R. Jesudason, S. Sato, Parameswaran, A.D. Araujo, A. Majumdar, P.G. Allen, E.B. Suki and B. Suki. Biophys. J. 99(9): 3076-83, 2010.

33. Autophagy protein LC3B activates extrinsic apoptosis during cigarette-smoke induced emphysema. Z. Chen, H. Lam, Y. Jin, HH. Kim, J. Cao, S. Lee, E. Ifedigbo, Parameswaran, S. Ryter and A. Choi. Proc. Natl. Acad. Sci USA. 107(44): 18880-5, 2010.

 

2009

34. Three-dimensional measurement of alveolar airspace volumes in normal and emphysematous lungs using micro-CT, Parameswaran, E.B. Suki, H. Hamakawa, A. Majumdar, P. Allen, B. Suki. J. Appl. Physiol. 107(2): 583-592, 2009.

35. Estimating the diameter of airways susceptible for collapse using crackle sound, A. Majumdar, Z. Hantos, J. Tolnai, Parameswaran, R. Tepper, and B. Suki. J. Appl. Physiol.,107(5):1504-12, 2009.

 

2008-2004

36. Quantitative characterization of airspace enlargement in emphysema. Parameswaran, A. Majumdar, S. Ito, A. M. Alencar, and B. Suki. J. Appl. Physiol. 100: 186-193, 2006.

37. Pattern of parenchymal destruction determines lung function decline. Parameswaran, A Majumdar, H. Hamakawa, and B. Suki. J. Appl. Physiol. 105(6):1984-1984, 2008.

38. Alveolar macrophage activation and an emphysema like phenotype in adiponectin deficient mice. R. Summer, F. Little, N. Ouchi, Y. Takemura, T. Aprahamian, D. Dwyer, K. Fitzsimmons, B. Suki, Parameswaran, A. Fine, K. Walsh. Am. J. Physiol.: Lung Cell Mol. Physiol. 294: L1035-L1042, 2008.

39. Early emphysema in the tight skin and the pallid mice: roles of microfibril associated glycoprotein, collagen and mechanical forces. S. Ito, E.B. Suki, J.M. Shipley, Parameswaran, A. Majumdar, B. Suki. Am. J. Respir. Cell Mol. Biol. 34(6):688-694, 2006.

40. Mechanics, nonlinearity, and failure strength of lung tissue in a mouse model of emphysema: possible role of collagen remodeling. Ito, E.P. Ingenito, K.K. Brewer, L.D. Black, H. Parameswaran, K.R. Lutchen, B. Suki. J. Appl. Physiol. 98: 503-511, 2005.

41. Tissue heterogeneity in the mouse lung: effects of elastase treatment. Ito, E.P. Ingenito, S. P. Arold, H. Parameswaran, N. T. Tgavalekos, K. R. Lutchen, and B. Suki. J. Appl. Physiol. 97: 204-212, 2004.

 

Invited Book Chapter

  1. Assessing Structure-Function Relations in Mice Using the Forced Oscillation Technique and Quantitative Histology. H Parameswaran and B. Suki Methods Mol Biol. 2017;1639:77-91.

Invited letter

  1. Morphological quantification of emphysema: A debate Parameswaran, A. Majumdar, S. Ito, A. M. Alencar, and B. Suki. J. Appl. Physiol. 100(4):1420-1421, 2006.

Students

Jun 07, 2021

Summer 2021 PEAK Experiences Awardees

Congratulations to the COE student recipients of the Summer 2021 PEAK Experiences Awards. The PEAK Experiences Awards are a progressively structured sequence of opportunities designed to support learners as they continue climbing to new heights of achievement in undergraduate research and creative endeavor throughout their Northeastern journeys. BASE CAMP AWARDS Ana Salichs, E’22, “Colorimetric Assays […]

Harikrishnan Parameswaran

Faculty

Mar 30, 2021

Parameswaran Receives NSF CAREER Award for Better Treatment of Asthma

Assistant Professor Harikrishnan Parameswaran, bioengineering, received a $600K NSF CAREER Award for “Elucidating the Role of Collective Cell-Matrix Interactions in the Mechanobiology of Airway Narrowing.” The research seeks to understand how the smooth muscle detects inhaled irritants and generates force at the cellular level to develop better treatment for people with asthma.

Students

Feb 08, 2021

Spring 2021 PEAK Experience Recipients

Congratulations to the COE student recipients of the Spring 2021 PEAK Experiences Awards. The PEAK Experiences Awards are a progressively structured sequence of opportunities designed to support learners as they continue climbing to new heights of achievement in undergraduate research and creative endeavor throughout their Northeastern journeys. PEAK Experience Ascent Awardees Ryan Brady, COE’22, Chemical […]

Harikrishnan Parameswaran

Faculty

Aug 17, 2020

Research on Extracellular Matrix Making Waves for Asthma Therapy

BioE Assistant Professor Harikrishnan Parameswaran’s research on “Intercellular communication controls agonist-induced calcium oscillations independently of gap junctions in smooth muscle cells” was published in Science Advances.

Faculty

Apr 09, 2019

FY20 TIER 1 Award Recipients

25 COE faculty and affiliates were recipients of FY20 TIER 1 Interdisciplinary Research Seed Grants for 18 different projects representing up to $900K dollars of investment in research.

Faculty

Jan 20, 2017

New Faculty Spotlight: Harikrishnan Parameswaran

Harikrishnan Parameswaran joins the Bioengineering department in January 2017 as an Assistant Professor.

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